Atherosclerosis is an inflammatory disease characterized by leukocyte infiltration,smooth muscle cell accumulation and neointima formation[1]. Activation and damage of the endothelial monolayer seems to trigger the de...Atherosclerosis is an inflammatory disease characterized by leukocyte infiltration,smooth muscle cell accumulation and neointima formation[1]. Activation and damage of the endothelial monolayer seems to trigger the development of the lesions. Initially,it was thought that the damaged endothelial cells were replaced by the adjacent intact endothelium.展开更多
Implanting artificial organelles in living cells is capable of correcting cellular dysfunctionalities for cell repair and biomedical applications. In this work, phase-separated bienzyme-loaded coacervate microdroplets...Implanting artificial organelles in living cells is capable of correcting cellular dysfunctionalities for cell repair and biomedical applications. In this work, phase-separated bienzyme-loaded coacervate microdroplets are established as a model of artificial membraneless organelles in endothelial dysfunctional cells for the cascade enzymatic production of nitric oxide(NO) with a purpose of correcting cellular NO deficiency. We prepared the coacervate microdroplets via liquid-liquid phase separation of oppositely charged polyelectrolytes, in which glucose oxidase/horseradish peroxidase-mediated cascade reaction was compartmented. After the coacervate microdroplets were implanted in NO-deficient dysfunctional cells, the compartments maintained a phase-separated liquid droplet structure, which facilitated a significant enhancement of NO production in the dysfunctional cells. The recovery of NO production was further exploited to inhibit clot formation in blood plasma located in the cell suspension. This demonstrated a proof-of-concept design of artificial organelles in dysfunctional cells for cell repair and anticoagulation-related medical applications. Our results demonstrate an approach for the construction of coacervate droplets through phase separation for the generation of artificial membraneless organelles, which can be designed to provide an array of functionalities in living organisms that have the potential to be used in the field of cell engineering and medical therapy.展开更多
Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of ti...Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly;however,the basic process of repair at the cell level is often neglected.Because the cell is the basic unit of organism structure and function;cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury.Then,damage to tissues and organs occurs with massive cell damage,apoptosis and even cell death.Thus,how to achieve the aim of perfect repair and regeneration?The basic process of tissue or organ repair and regeneration should involve repair of cells first,then tissues and organs.In this manuscript,it is my consideration about how to repair the cell first,then regenerate the tissues and organs.展开更多
Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role th...Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis.Much of this research has focused on the use of the airway repair model to study response to injury.In this review,we discuss the primary evidence of the role that cancer stem cells play in lung cancer development.The implications of a stem cell origin of lung cancer are reviewed,and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.展开更多
The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively partici...The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.展开更多
Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusiv...Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.展开更多
OECs for spinal cord repair: Is repairing the iniured spinal cord by olfactory ensheathing cell (OEC) transplantation pos- sible? A recent human trial in which a paralysed man regained some function after transpla...OECs for spinal cord repair: Is repairing the iniured spinal cord by olfactory ensheathing cell (OEC) transplantation pos- sible? A recent human trial in which a paralysed man regained some function after transplantation of partially purified OECs suggests that this therapy may be a successful approach (Ta- bakow et al., 2014). In another human trial in which olfactory mucosa lamina propria was transplanted, patients recovered some motor and sensory function (Wang et al., 2015). While these results show promise, it is clear that improvements are needed to provide patients with increased functional output. Strategies to improve the therapeutic use of OECs may include improving the purification of the OECs used for transplantation, using them in combination with growth factors to combat the inhibitory environment and improve anon growth, the use of nerve bridges, advanced physiotherapy and the use of exo- skeleton robotics to reinforce functional connections. Of all these approaches, it is probably is primarily addressed to ensure crucial that the purity of OECs consistency in outcomes.展开更多
Objective To explore repair of spinal cord injury by neural stem cells (NSCs) modified with brain derived neurotrophic factor (BDNF) gene (BDNF-NSCs) in rats. Methods Neural stem cells modified with BDNF gene we...Objective To explore repair of spinal cord injury by neural stem cells (NSCs) modified with brain derived neurotrophic factor (BDNF) gene (BDNF-NSCs) in rats. Methods Neural stem cells modified with BDNF gene were transplanted into the complete transection site of spinal cord at the lumbar 4 (L4) level in rats. Motor function of rats' hind limbs was observed and HE and X-gal immunoeytochemical staining, in situ hybridization, and retrograde HRP tracing were also performed. Results BDNF-NSCs survived and integrated well with host spinal cord. In the transplant group, some X-gal positive, NF-200 positive, GFAP positive, BDNF positive, and BDNF mRNA positive cells, and many NF-200 positive nerve fibers were observed in the injury site. Retrograde HRP tracing through sciatic nerve showed some HRP positive cells and nerve fibers near the rostral side of the injury one month after transplant and with time, they increased in number. Examinations on rats' motor function and behavior demonstrated that motor function of rats' hind limbs improved better in the transplant group than the injury group. Conclusion BDNF-NSCs can survive, differentiate, and partially integrate with host spinal cord, and they significantly ameliorate rats' motor function of hind limbs, indicating their promising role in repairing spinal cord injury.展开更多
Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy aft...Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.展开更多
Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair u...Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.展开更多
BACKGROUND: Animal experiments and clinical studies about tissue engineering method applied to repair nerve injury mainly focus on seeking ideal artificial nerve grafts, nerve conduit and seed cells. Autologous nerve...BACKGROUND: Animal experiments and clinical studies about tissue engineering method applied to repair nerve injury mainly focus on seeking ideal artificial nerve grafts, nerve conduit and seed cells. Autologous nerve, allogeneic nerve and xenogeneic nerve are used to bridge nerve defects, it is one of the methods to promote the repair of nerve injury by culturing and growing Schwann cells, which can secrete various neurotrophic factor activities, in the grafts. OBJECTIVE : To observe the effect of acellular nerve grafts co-cultured with Schwann cells in repairing defects of sciatic nerve. DESIGN: An observational comparative study.SETTING: Tissue Engineering Laboratory of China Medical University.MATERIALS: The experiment was carried out in the Tissue Engineering Laboratory of China Medical University between April 2004 and April 2005. Forty neonatal Sprague-Dawley rats of 5-8 days (either males or females) and 24 male Wistar rats of 180-220 g were provided by the experimental animal center of China Medical University. METHODS: ① Culture of Schwann cells: The bilateral sciatic nerves and branchial plexus were isolated from the 40 neonatal SD rats. The sciatic nerves were enzymatically digested with collagenase and dispase, isolatd, purified and cultured with the method of speed-difference adhersion, and identified with the SABC immunohistochemical method. ② Model establishment: In vitro Schwann cells were microinjected into 10-mm long acellular nerve grafts repairing a surgically created gap in the rat sciatic nerve. According to the different grafted methods, the animals were randomly divided into three groups: autografts (n=8), acellular nerve grafts (n=8), or acellular nerve grafts with Schwann cells (n=8). ③ The regenerated nerve fiber number and average diameter of myeline sheath after culture were statistically anlayzed. MAIN OUTCOME MEASURES: ① The regenerated nerve ultrastructure, total number and density of myelinated nerve fibers, and the thickness of myeline sheath were observed under electron microscope. ② The images were processed with the Mias-1000 imaging analytical system to calculate the number of myelinated nerve fibers, and the thickness of myeline sheath. RESULTS: All the 24 Wistar rats were involved in the analysis of results. ① Results observed under transmission electron microscope: The regenerated myelinated nerve fibers in the group of acellular nerve grafts with Schwann cells were more even than those in the group of acellular nerve grafts, the number of myelinated nerve fibers and thickness of myelin sheath were close to those in the allografts group (P 〉 0.05), but significantly different from those in the group of acellular nerve grafts (P 〈 0.05). ② Results observed under scanning electron microscope: A great amount of Schwann cells with two polars were observed in the group of grafts with Schwann cells, the feature of cultured Schwann cells showed shoulder by shoulder, head to head. ③ The number of myelinated nerve fibers and thickness of myelin sheath analyzed by Mias-1000 imaging system in the group of acellular nerve grafts with Schwann cells were close to those in the autografts group (P 〉 0.05), but significantly different from those in the group of acellular nerve grafts (P 〈 0.05).CONCLUSION: Host axonal regeneration is significantly increased after implant of acellular nerve grafts. Acellular nerve grafts with Schwann cells offers a novel approach for repairing the gap of nerve defect.展开更多
Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells(i PSCs) theoretically provide an unlimited number of specialized cells which could be used in articu...Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells(i PSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from i PSCs have usually been formed in condensed cell bodies(resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from i PSCs are problematic but solutions to these problems are on the horizon. These solutions will make i PSCs a viable alternative for articular cartilage repair in the near future.展开更多
Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and ...Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein(BMP) signalling and depend on BMP-mediated Indian hedgehog(IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand(RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog(Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMPmediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.展开更多
A novel double-layer collagen membrane with unequal pore sizes in each layer was designed and tested in this study. The inner, loose layer has about 100-μm-diameter pores, while the outer, compact layer has about 10-...A novel double-layer collagen membrane with unequal pore sizes in each layer was designed and tested in this study. The inner, loose layer has about 100-μm-diameter pores, while the outer, compact layer has about 10-μm-diameter pores. In a rat model of incomplete spinal cord injury, a large number of neural stem cells were seeded into the loose layer, which was then adhered to the injured side, and the compact layer was placed against the lateral side. The results showed that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes promoted the differentiation of neural stem cells, attenuated the pathological lesion, and signiifcantly improved the motor function of the rats with incomplete spinal cord injuries. These experimental ifndings suggest that the transplantation of neural stem cells in a double-lay-er collagen membrane with unequal pore sizes is an effective therapeutic strategy to repair an injured spinal cord.展开更多
Three articles regarding transplantation of umbilical cord mesenchmal stem cells alone or in combination with Schwann cells and feridex and polylysine complex-labeled bone marrow stromal cell transplantation (MRI tra...Three articles regarding transplantation of umbilical cord mesenchmal stem cells alone or in combination with Schwann cells and feridex and polylysine complex-labeled bone marrow stromal cell transplantation (MRI tracing) for repair of sciatic nerve injury were reported in Neural Regeneration展开更多
Stem cells have shown great potential in vascular repair.Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion,proliferation,migration,and differentiation ...Stem cells have shown great potential in vascular repair.Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion,proliferation,migration,and differentiation of stem cells via serious signaling pathways.The enrichment and differentiation of stem cells play an important role in the angiogenesis and maintenance of vascular homeostasis.In normal tissues,blood flow directly affects the microenvironment of vascular endothelial cells(ECs);in pathological status,the abnormal interactions between blood flow and vessels contribute to the injury of vessels.Next,the altered mechanical forces are transduced into cells by mechanosensors to trigger the reformation of vessels.This process occurs when signaling pathways related to EC differentiation are initiated.Hence,a deep understanding of the responses of stem cells to mechanical stresses and the underlying mechanisms involved in this process is essential for clinical translation.In this the review,we provide an overview of the role of stem cells in vascular repair,outline the performance of stem cells under the mechanical stress stimulation,and describe the related signaling pathways.展开更多
Background: Wound healing is a process of cell-cell interaction and cell-extracellular matrix interaction. Dermal multipotent stem cells (dMSCs) have the abilities to promote survival and wound healing, but the potent...Background: Wound healing is a process of cell-cell interaction and cell-extracellular matrix interaction. Dermal multipotent stem cells (dMSCs) have the abilities to promote survival and wound healing, but the potential function of dMSCs in wound healing, particularly in the initiation of wound repair, has not been fully understood. Methods: dMSCs and fibroblasts were isolated from neonatal rat dermis and were further purified and expanded. The cell cycles were determined with flow cytometry, while the radiosensitivity was measured by MTT assay. Rats were wounded with a 7-cm incision on the back skin and the wound fluids were collected by inserting two pieces of sterile polyvinyl alcohol sponge (1 cmin diameter and0.4 cmin thickness) subcutaneously into the dorsum of each rat through the midline of incision on the 1st, 2nd, 3rd and 4th day after incision. The effects of wound fluids on the proliferation of dMSCs and fibroblasts were measured with MTT assays. dMSC’s abilities of adhesion and attachment and its migration in response to wound fluids collected on the 1st day after incision were explored by measuring the percentage of floating cells and the cells migrated into wounding area in vitro, respectively. Results: The isolated dMSCs were morphologically homogenous and highly proliferative. Most of the cultured dMSCs were quiescent with few apoptotic cells. Compared with fibroblasts, dMSCs were more sensitive to radiation and more proliferative in response to wound fluids, especially to the wound fluids collected on the 1st day after wounding. Moreover, their abilities to attach, adhere and migrate were significantly enhanced with the early-phase wound fluids. Conclusions: As primitive stem cells, dMSCs are very responsive to wound fluids, which suggests dMSCs’ important role in wound healing, especially in initiating wound repair.展开更多
The aim of the present study was to investigate and compare the bone formation capacity with three different grafts. Four millimeter segmental defects were created in adult rat tibias and were either left empty (cont...The aim of the present study was to investigate and compare the bone formation capacity with three different grafts. Four millimeter segmental defects were created in adult rat tibias and were either left empty (control defects) or implanted with (1) nano-hydroxyapatite/collagen/PIA (nHAC/PIA) composite, (2) nHAC/ PIA composite added with bone marrow mesenchymal tem cells ( BMSCs ), ( 3 ) nHAC/ PIA composite added with bone morphogenetic protein 2 ( BMP- 2). Radiographs of the defects were taken weekly post-surgery. After 1 or 2 months, the rats were eathaaized. Histologic analyses were performed on the harvested tissue. nHAC/ PIA composite could enhance the repair of rat tibia segmental defects. Addition of BMSCs or BMP- 2 to nHAC/ PIA led to an increase in osteogenesis, nHAC/ PIA composite could be an Meal alternative bone-grafi material and it could also be used as an Meal carrier of BMSCs or BMP- 2.展开更多
基金supported by Grants from British Heart Foundation and Oak Foundation
文摘Atherosclerosis is an inflammatory disease characterized by leukocyte infiltration,smooth muscle cell accumulation and neointima formation[1]. Activation and damage of the endothelial monolayer seems to trigger the development of the lesions. Initially,it was thought that the damaged endothelial cells were replaced by the adjacent intact endothelium.
基金supported by the National Natural Science Foundation of China(21735002,22177032,32101082)the Science Fund for Distinguished Young Scholars of Hunan Province(2021JJ10013)+1 种基金the Hunan Province Innovative Talent Funding for Postdoctoral Fellows(2021RC2059)the Postdoctoral Science Foundation of China(2021TQ0103,2021M690957).
文摘Implanting artificial organelles in living cells is capable of correcting cellular dysfunctionalities for cell repair and biomedical applications. In this work, phase-separated bienzyme-loaded coacervate microdroplets are established as a model of artificial membraneless organelles in endothelial dysfunctional cells for the cascade enzymatic production of nitric oxide(NO) with a purpose of correcting cellular NO deficiency. We prepared the coacervate microdroplets via liquid-liquid phase separation of oppositely charged polyelectrolytes, in which glucose oxidase/horseradish peroxidase-mediated cascade reaction was compartmented. After the coacervate microdroplets were implanted in NO-deficient dysfunctional cells, the compartments maintained a phase-separated liquid droplet structure, which facilitated a significant enhancement of NO production in the dysfunctional cells. The recovery of NO production was further exploited to inhibit clot formation in blood plasma located in the cell suspension. This demonstrated a proof-of-concept design of artificial organelles in dysfunctional cells for cell repair and anticoagulation-related medical applications. Our results demonstrate an approach for the construction of coacervate droplets through phase separation for the generation of artificial membraneless organelles, which can be designed to provide an array of functionalities in living organisms that have the potential to be used in the field of cell engineering and medical therapy.
文摘Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly;however,the basic process of repair at the cell level is often neglected.Because the cell is the basic unit of organism structure and function;cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury.Then,damage to tissues and organs occurs with massive cell damage,apoptosis and even cell death.Thus,how to achieve the aim of perfect repair and regeneration?The basic process of tissue or organ repair and regeneration should involve repair of cells first,then tissues and organs.In this manuscript,it is my consideration about how to repair the cell first,then regenerate the tissues and organs.
文摘Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis.Much of this research has focused on the use of the airway repair model to study response to injury.In this review,we discuss the primary evidence of the role that cancer stem cells play in lung cancer development.The implications of a stem cell origin of lung cancer are reviewed,and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.
文摘The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.
文摘Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.
基金supported by a Perry Cross Spinal Research Foundation grant to JSJan Australian Research Council Discovery Grant DP150104495 to JE and JSJ
文摘OECs for spinal cord repair: Is repairing the iniured spinal cord by olfactory ensheathing cell (OEC) transplantation pos- sible? A recent human trial in which a paralysed man regained some function after transplantation of partially purified OECs suggests that this therapy may be a successful approach (Ta- bakow et al., 2014). In another human trial in which olfactory mucosa lamina propria was transplanted, patients recovered some motor and sensory function (Wang et al., 2015). While these results show promise, it is clear that improvements are needed to provide patients with increased functional output. Strategies to improve the therapeutic use of OECs may include improving the purification of the OECs used for transplantation, using them in combination with growth factors to combat the inhibitory environment and improve anon growth, the use of nerve bridges, advanced physiotherapy and the use of exo- skeleton robotics to reinforce functional connections. Of all these approaches, it is probably is primarily addressed to ensure crucial that the purity of OECs consistency in outcomes.
文摘Objective To explore repair of spinal cord injury by neural stem cells (NSCs) modified with brain derived neurotrophic factor (BDNF) gene (BDNF-NSCs) in rats. Methods Neural stem cells modified with BDNF gene were transplanted into the complete transection site of spinal cord at the lumbar 4 (L4) level in rats. Motor function of rats' hind limbs was observed and HE and X-gal immunoeytochemical staining, in situ hybridization, and retrograde HRP tracing were also performed. Results BDNF-NSCs survived and integrated well with host spinal cord. In the transplant group, some X-gal positive, NF-200 positive, GFAP positive, BDNF positive, and BDNF mRNA positive cells, and many NF-200 positive nerve fibers were observed in the injury site. Retrograde HRP tracing through sciatic nerve showed some HRP positive cells and nerve fibers near the rostral side of the injury one month after transplant and with time, they increased in number. Examinations on rats' motor function and behavior demonstrated that motor function of rats' hind limbs improved better in the transplant group than the injury group. Conclusion BDNF-NSCs can survive, differentiate, and partially integrate with host spinal cord, and they significantly ameliorate rats' motor function of hind limbs, indicating their promising role in repairing spinal cord injury.
文摘Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.
基金This work was supported by the grants from National Natural Science Foundation of China(Nos.30170208,30623003 and 30170208)from the Ministry of Science and Technology,China(No.2001AA233031 and No.2001CB510205)from US NIH(CA50519)(to DJ Chen).
文摘Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.
基金the National Natural Science Foundation of China, No. 30070775 a grant from the Scientific Research Foundation of Liaoning Department of Education, No. 2005L5371
文摘BACKGROUND: Animal experiments and clinical studies about tissue engineering method applied to repair nerve injury mainly focus on seeking ideal artificial nerve grafts, nerve conduit and seed cells. Autologous nerve, allogeneic nerve and xenogeneic nerve are used to bridge nerve defects, it is one of the methods to promote the repair of nerve injury by culturing and growing Schwann cells, which can secrete various neurotrophic factor activities, in the grafts. OBJECTIVE : To observe the effect of acellular nerve grafts co-cultured with Schwann cells in repairing defects of sciatic nerve. DESIGN: An observational comparative study.SETTING: Tissue Engineering Laboratory of China Medical University.MATERIALS: The experiment was carried out in the Tissue Engineering Laboratory of China Medical University between April 2004 and April 2005. Forty neonatal Sprague-Dawley rats of 5-8 days (either males or females) and 24 male Wistar rats of 180-220 g were provided by the experimental animal center of China Medical University. METHODS: ① Culture of Schwann cells: The bilateral sciatic nerves and branchial plexus were isolated from the 40 neonatal SD rats. The sciatic nerves were enzymatically digested with collagenase and dispase, isolatd, purified and cultured with the method of speed-difference adhersion, and identified with the SABC immunohistochemical method. ② Model establishment: In vitro Schwann cells were microinjected into 10-mm long acellular nerve grafts repairing a surgically created gap in the rat sciatic nerve. According to the different grafted methods, the animals were randomly divided into three groups: autografts (n=8), acellular nerve grafts (n=8), or acellular nerve grafts with Schwann cells (n=8). ③ The regenerated nerve fiber number and average diameter of myeline sheath after culture were statistically anlayzed. MAIN OUTCOME MEASURES: ① The regenerated nerve ultrastructure, total number and density of myelinated nerve fibers, and the thickness of myeline sheath were observed under electron microscope. ② The images were processed with the Mias-1000 imaging analytical system to calculate the number of myelinated nerve fibers, and the thickness of myeline sheath. RESULTS: All the 24 Wistar rats were involved in the analysis of results. ① Results observed under transmission electron microscope: The regenerated myelinated nerve fibers in the group of acellular nerve grafts with Schwann cells were more even than those in the group of acellular nerve grafts, the number of myelinated nerve fibers and thickness of myelin sheath were close to those in the allografts group (P 〉 0.05), but significantly different from those in the group of acellular nerve grafts (P 〈 0.05). ② Results observed under scanning electron microscope: A great amount of Schwann cells with two polars were observed in the group of grafts with Schwann cells, the feature of cultured Schwann cells showed shoulder by shoulder, head to head. ③ The number of myelinated nerve fibers and thickness of myelin sheath analyzed by Mias-1000 imaging system in the group of acellular nerve grafts with Schwann cells were close to those in the autografts group (P 〉 0.05), but significantly different from those in the group of acellular nerve grafts (P 〈 0.05).CONCLUSION: Host axonal regeneration is significantly increased after implant of acellular nerve grafts. Acellular nerve grafts with Schwann cells offers a novel approach for repairing the gap of nerve defect.
文摘Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells(i PSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from i PSCs have usually been formed in condensed cell bodies(resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from i PSCs are problematic but solutions to these problems are on the horizon. These solutions will make i PSCs a viable alternative for articular cartilage repair in the near future.
基金supported by grants from the National Institute of Dental and Craniofacial Research, NIH (supported by R01 DE026339)
文摘Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein(BMP) signalling and depend on BMP-mediated Indian hedgehog(IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand(RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog(Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMPmediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.
文摘A novel double-layer collagen membrane with unequal pore sizes in each layer was designed and tested in this study. The inner, loose layer has about 100-μm-diameter pores, while the outer, compact layer has about 10-μm-diameter pores. In a rat model of incomplete spinal cord injury, a large number of neural stem cells were seeded into the loose layer, which was then adhered to the injured side, and the compact layer was placed against the lateral side. The results showed that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes promoted the differentiation of neural stem cells, attenuated the pathological lesion, and signiifcantly improved the motor function of the rats with incomplete spinal cord injuries. These experimental ifndings suggest that the transplantation of neural stem cells in a double-lay-er collagen membrane with unequal pore sizes is an effective therapeutic strategy to repair an injured spinal cord.
文摘Three articles regarding transplantation of umbilical cord mesenchmal stem cells alone or in combination with Schwann cells and feridex and polylysine complex-labeled bone marrow stromal cell transplantation (MRI tracing) for repair of sciatic nerve injury were reported in Neural Regeneration
基金Supported by the National Natural Science Foundation of China,No.11672197 and No.81702171the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen,No.201806081018272960
文摘Stem cells have shown great potential in vascular repair.Numerous evidence indicates that mechanical forces such as shear stress and cyclic strain can regulate the adhesion,proliferation,migration,and differentiation of stem cells via serious signaling pathways.The enrichment and differentiation of stem cells play an important role in the angiogenesis and maintenance of vascular homeostasis.In normal tissues,blood flow directly affects the microenvironment of vascular endothelial cells(ECs);in pathological status,the abnormal interactions between blood flow and vessels contribute to the injury of vessels.Next,the altered mechanical forces are transduced into cells by mechanosensors to trigger the reformation of vessels.This process occurs when signaling pathways related to EC differentiation are initiated.Hence,a deep understanding of the responses of stem cells to mechanical stresses and the underlying mechanisms involved in this process is essential for clinical translation.In this the review,we provide an overview of the role of stem cells in vascular repair,outline the performance of stem cells under the mechanical stress stimulation,and describe the related signaling pathways.
文摘Background: Wound healing is a process of cell-cell interaction and cell-extracellular matrix interaction. Dermal multipotent stem cells (dMSCs) have the abilities to promote survival and wound healing, but the potential function of dMSCs in wound healing, particularly in the initiation of wound repair, has not been fully understood. Methods: dMSCs and fibroblasts were isolated from neonatal rat dermis and were further purified and expanded. The cell cycles were determined with flow cytometry, while the radiosensitivity was measured by MTT assay. Rats were wounded with a 7-cm incision on the back skin and the wound fluids were collected by inserting two pieces of sterile polyvinyl alcohol sponge (1 cmin diameter and0.4 cmin thickness) subcutaneously into the dorsum of each rat through the midline of incision on the 1st, 2nd, 3rd and 4th day after incision. The effects of wound fluids on the proliferation of dMSCs and fibroblasts were measured with MTT assays. dMSC’s abilities of adhesion and attachment and its migration in response to wound fluids collected on the 1st day after incision were explored by measuring the percentage of floating cells and the cells migrated into wounding area in vitro, respectively. Results: The isolated dMSCs were morphologically homogenous and highly proliferative. Most of the cultured dMSCs were quiescent with few apoptotic cells. Compared with fibroblasts, dMSCs were more sensitive to radiation and more proliferative in response to wound fluids, especially to the wound fluids collected on the 1st day after wounding. Moreover, their abilities to attach, adhere and migrate were significantly enhanced with the early-phase wound fluids. Conclusions: As primitive stem cells, dMSCs are very responsive to wound fluids, which suggests dMSCs’ important role in wound healing, especially in initiating wound repair.
文摘The aim of the present study was to investigate and compare the bone formation capacity with three different grafts. Four millimeter segmental defects were created in adult rat tibias and were either left empty (control defects) or implanted with (1) nano-hydroxyapatite/collagen/PIA (nHAC/PIA) composite, (2) nHAC/ PIA composite added with bone marrow mesenchymal tem cells ( BMSCs ), ( 3 ) nHAC/ PIA composite added with bone morphogenetic protein 2 ( BMP- 2). Radiographs of the defects were taken weekly post-surgery. After 1 or 2 months, the rats were eathaaized. Histologic analyses were performed on the harvested tissue. nHAC/ PIA composite could enhance the repair of rat tibia segmental defects. Addition of BMSCs or BMP- 2 to nHAC/ PIA led to an increase in osteogenesis, nHAC/ PIA composite could be an Meal alternative bone-grafi material and it could also be used as an Meal carrier of BMSCs or BMP- 2.