Modified approach of regenerative treatment for distal intrabony defect beneath non-keratinized mucosa at terminal molar:A case report

BACKGROUND Intrabony defects beneath non-keratinized mucosa are frequently observed at the distal site of terminal molars.Consequently,the application of regenerative treatment using the modified wedge-flap technique is considered impractical for these specific dental conditions.CASE SUMMARY This article proposes a modified surgical procedure aimed at exposing the distal intrabony defect by making a vertical incision in the keratinized buccal gingiva.The primary objective is to maintain gingival flap stability,thereby facilitating periodontal regeneration.The described technique was successfully employed in a case involving the left mandibular second molar,which presented with an intrabony defect without keratinized gingiva at the distal site.In this case,an incision was made on the disto-buccal gingival tissue,creating a tunnel-like separation of the distal non-keratinized soft tissue to expose the intrabony defect.Subsequently,bone grafting and guided tissue regeneration surgeries were performed,resulting in satisfactory bone fill at 9 mo postoperatively.CONCLUSION This technique offers a regenerative opportunity for the intrabony defects beneath non-keratinized mucosa and is recommended for further research.

Generalized periodontitis treated with periodontal,orthodontic,and prosthodontic therapy:A case report

BACKGROUND Generalized periodontitis is a severe periodontal disease characterized by rapid periodontal destruction in healthy persons.This case report describes the treatment of a severe crowding,large overjet,and occlusal collapse due to the loss of anterior guidance with generalized periodontitis.CASE SUMMARY A 35-year-old female patient with a chief complaint of crowding and maxillary protrusion was diagnosed with generalized periodontitis by clinical and radiographic examinations.To improve crowding and overjet,orthodontic treatment was performed after basic periodontal therapy.Severely damaged upper right lateral incisor and left canine were extracted,and lower right first premolar and left second premolar were also removed to treat severe crowding.After orthodontic treatment,periodontal flap surgery for upper left molars and guided tissue regeneration for the lower left second molar was performed.Then,a dental implant was inserted in the upper left canine legion.The esthetics of the maxillary anterior tooth was improved by prosthetic restorations.The treatment result showed a well-improved occlusion with proper anterior guidance and healthy periodontal tissue after a retention period of 10 years.CONCLUSION Periodontal,orthodontic,and prosthodontic treatments are extremely useful to improve function and stable periodontal tissue for generalized periodontitis.

A review of regenerative therapies as penile rehabilitation in men following primary prostate cancer treatment:Evidence for erectile restoration and cavernous nerve regeneration

Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate cancer(PCa)treatment and PCa survivorship.Methods:This narrative clinical review paper summarizes what is currently known about various modalities of regenerative therapy in restoring spontaneous erectile function(EF)in men following PCa treatment with an emphasis on penile rehabilitation strategies.Results:Conventional medical therapy often does not reverse underlying endothelial dysfunction or promote neuro-vasculogenesis to preserve penile health in men with ED.Over the past decade,there has been considerable interest in the role of regenerative therapy to restore endothelial dysfunction and ED without future dependency on medical therapy.Regenerative therapy can be classified into cellular-based(immunomodulators,stem cells,and platelet-rich plasma),biomaterials(nerve graft transfer),and device-related technology(low-intensity shockwave).Although published literature shows early promise in the role of regenerative technology for ED,there is a paucity of high-quality clinical trials in the setting of penile rehabilitation and PCa survivorship to support their use as standard care and be adopted in clinical guidelines.

Still'dwelling in the possibility'-critical update on stem cell therapy for acute on chronic liver failure

Stem cells therapy could improve survival in patients with liver failure.Studies on stem cell therapy and related growth factors in decompensated cirrhosis has been on the forefront but has shown heterogenous results.Recent high-quality studies have shown a lack of efficacy and safety.Patients with acute-on-chronic liver failure(ACLF)are a unique group with high mortality in the short-term associated with rapid onset extrahepatic organ failures.In these patients,there is an urgent need to identify treatments that can improve liver cell function and mass,prevent sepsis/organ failure,ameliorate systemic inflammation,and increase transplant-free survival.Stem cells are a novel treatment in ACLF but with unclear efficacy and safety.In this narrative review,we discuss the basics of liver regeneration in patients with ACLF and update current clinical status of stem cell use in patients with ACLF for improving our understanding of future directions.

Novel approaches for the development of peripheral nerve regenerative therapies

Schwann cells are the myelinating glial cells of the peripheral nervous system（PNS）.By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated-a process referred to as saltatory signal propagation.Apart from this prominent physiological function,these cells also exert important pathophysiological roles in PNS injuries or dis- eases. In contrast to the central nervous system （CNS）, the adult PNS retains a remarkably high degree of intrinsic re- generation. As a consequence, transected axons and dam- aged myelin sheaths can be repaired and nerve functional- ity can be restored. This spontaneous regenerative capacity depends on （inter） actions of macrophages, neurons, and Schwann cells.

Melatonin,tunneling nanotubes,mesenchymal cells,and tissue regeneration

Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.

Human hair follicle-derived mesenchymal stem cells:Isolation,expansion,and differentiation

Hair follicles are easily accessible skin appendages that protect against cold and potential injuries.Hair follicles contain various pools of stem cells,such as epithelial,melanocyte,and mesenchymal stem cells(MSCs)that continuously self-renew,differentiate,regulate hair growth,and maintain skin homeostasis.Recently,MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential.In this review,we describe the applications of human hair follicle-derived MSCs(hHF-MSCs)in tissue engineering and regenerative medicine.We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail.We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages,including supplementation of growth factors,3D suspension culture technology,and 3D aggregates of MSCs.In addition,we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels,regenerated hair follicles,induced red blood cells,and induced pluripotent stem cells.In summary,the abundance,convenient accessibility,and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.

Disease modifying treatment of spinal cord injury with directly reprogrammed neural precursor cells in non-human primates

BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.

Therapeutic application of stem cells in gastroenterology:An up-date

Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastro-enterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immunemediated conditions,further studies are needed to fully understand the biology of stem cellsand carefully assess their put ativeonco- genicproperties.Moreover,there searchonstemcellsarousesferventethical,socialandpoliticaldebate.TheItalianSocietyofGastroenterologysponsoredaworkshoponstemcellsheldinVeronaduringtheⅩⅥCongressoftheFederationofItalianSocietiesofDigestiveDiseases(March 6-9,2010).Here,we report on the issues discussed,including liver and intestinal diseases that may benefit from stemcell therapy,the biology of hepatic and intestinal tissue repair,and stem cell usage inclinical trials.

Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and repair.The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal.With the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction.It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial infarction.However,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further explained.It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration.Here,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration.In addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation.Ultimately,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

Current status of cell-mediated regenerative therapies for human spinal cord injury

During the past decade, significant advances have been made in refinements for regenerative therapies following human spinal cord injury （SCI）. Positive results have been achieved with different types of cells in various clinical studies of SCI. In this review, we summarize recently-completed clinical trials using cell- mediated regenerative therapies for human SCI, together with ongoing trials using neural stem cells. Specifically, clinical studies published in Chinese journals are included. These studies show that current transplantation therapies are relatively safe, and have provided varying degrees of neurological recovery. However, many obstacles exist, hindering the introduction of a specific clinical therapy, including complications and their causes, selection of the target population, and optimization of transplantation material. Despite these and other challenges, with the collaboration of research groups and strong support from various organizations, cell-mediated regenerative therapies will open new perspectives for SCI treatment.

Developing Thick Cardiac Tissue with a Multilayer Fiber Sheet for Treating Myocardial Infarction

Human-induced pluripotent stem cell (hiPSC)-derived cardiac patches have been extensively used for treating myocardialinfarction and have shown potential for clinical application. However, the limited patch thickness can hamper its therapeuticeffect. We previously developed a fibrous scaffold that allowed the formation of well-organized cardiac tissue constructs. Inthe present study, based on the above technology, we developed a three-dimensional multilayer fibrous scaffold with dynamicperfusion, on which approximately 20 million hiPSC-derived cardiomyocytes (CMs) could be seeded in a single step andorganized into 1 mm thick and viable tissue. The multilayer cardiac tissue demonstrated enhanced contractile properties andupregulated cytokine secretion compared with the control group. Notably, when used on the myocardial infarction model,the multilayer group showed improved functional recovery and less fibrosis. These results indicated that the appropriatehiPSC-CM dose requires careful evaluation in developing clinical therapy. The multilayer cardiac tissue group demonstratedsignificant improvement than the control group, indicating that higher doses of transplanted cells may have improvedtherapeutic effects in treating myocardial infarction.

Emerging liver organoid platforms andtechnologies

Building human organs in a dish has been a long term goal of researchers in pursue of physiologically relevantmodels of human disease and for replacement of worn out and diseased organs. The liver has been an organ ofinterest for its central role in regulating body homeostasis as well as drug metabolism. An accurate liver replicashould contain the multiple cell types found in the organ and these cells should be spatially organized to resembletissue structures. More importantly, the in vitro model should recapitulate cellular and tissue level functions.Progress in cell culture techniques and bioengineering approaches have greatly accelerated the development ofadvance 3-dimensional (3D) cellular models commonly referred to as liver organoids. These 3D models describedrange from single to multiple cell type containing cultures with diverse applications from establishing patientspecificliver cells to modeling of chronic liver diseases and regenerative therapy. Each organoid platform isadvantageous for specific applications and presents its own limitations. This review aims to provide acomprehensive summary of major liver organoid platforms and technologies developed for diverse applications.