Crohn's disease(CD)is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract.The etiology of CD is unknown;however,genetic,epigenetic,environmental,and lifestyle factors could ...Crohn's disease(CD)is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract.The etiology of CD is unknown;however,genetic,epigenetic,environmental,and lifestyle factors could play an essential role in the onset and establishment of the disease.CD results from immune dysregulation due to loss of the healthy symbiotic relationship between host and intestinal flora and or its antigens.It affects both sexes equally with a male to female ratio of 1.0,and its onset can occur at any age,but the diagnosis is most commonly observed in the range of 20 to 40 years of age.CD diminishes quality of life,interferes with social activities,traumatizes due to the stigma of incontinence,fistulae,strictures,and colostomies,and in severe cases,affects survival when compared to the general population.Symptoms fluctuate between periods of remission and activity in which complications such as fistulas,strictures,and the need for bowel resection,surgery,and colostomy implantation make up the most severe aspects of the disease.CD can be progressive and the complications recurrent despite treatment with anti-inflammatory drugs,corticosteroids,immunosuppressants,and biological agents.However,over time many patients become refractory without treatment alternatives,and in this scenario,hematopoietic stem cell transplantation(HSCT)has emerged as a potential treatment option.The rationale for the use of HSCT for CD is anchored in animal studies and human clinical trials where HSCT could reset a patient's immune system by eliminating disease-causing effector cells and upon immune recovery increase regulatory and suppressive immune cells.Autologous HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without CD34+selection has been to date the most common transplant conditioning regimen adopted.In this review we will address the current situation regarding CD treatment with HSCT and emphasize the medical,ethical,and legal aspects that permeate the procedure in Brazil.展开更多
It is well known that to achieve an acceptable engraftment and survival in stem cell therapy, an human leukocyte antigens(HLA) identical stem cell transplant is strongly required. However, the availability of the HLA ...It is well known that to achieve an acceptable engraftment and survival in stem cell therapy, an human leukocyte antigens(HLA) identical stem cell transplant is strongly required. However, the availability of the HLA matched donors even among family members is extremely limited, so preimplantation HLA typing provides an attractive practical tool of stem cell therapy for children requiring HLA matched stem cell transplantation. The present experience of preimplantation genetic diagnosis(PGD) for HLA typing of over one thousand cases shows that PGD provides the at-risk couples with the option to establish an unaffected pregnancy, which may benefit the affected member of the family with hemoglobinopathies, immunodeficiencies and other congenital or acquired bone marrow failures. Despite ethical issues involved in preimplantation HLA typing, the data presented below show an extremely high attractiveness of this option for the couples with affected children requiring HLA compatible stem cell transplantation.展开更多
BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeuti...BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.展开更多
Background It has been indicated that autologous hematopoietic stem cell transplantation （AHST） is a promising treatment to adults with type 1 diabetes, however, the application of AHST therapy to children with type...Background It has been indicated that autologous hematopoietic stem cell transplantation （AHST） is a promising treatment to adults with type 1 diabetes, however, the application of AHST therapy to children with type 1 diabetes still needs more data. The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes. Methods This 1：2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology, Beijing Children＇s Hospital from 2009-2010. The case group included 14 patients, who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010. The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization. We compared the baseline and follow-up data of them, including ketoacidosis onset, clinical variables （glycosylated hemoglobin （HbAlc）, insulin dosage and serum C-peptide）. Results The clinical characteristics of the patients was comparable between the case group and the control group. At 6-12 months （（10.7±4.2） months） after AHST treatment, we found 11 patients in the case group did not stop the insulin therapy, three cases stopped insulin treatment for 2, 3 and 11 months, respectively. No diabetic ketoacidosis （DKA） occurred after transplantation in all the patients in the case group. HbAlc in the control group was significant lower than that in the case group （P 〈0.01）, while the insulin dosage and serum C-peptide were not significant different between the two groups （P 〉0.05）. In order to eliminate the honeymoon effect, we performed final follow-up at the 3-5 years （（4.2±1.8） years） after AHST treatment, and found that HbAlc in the control group was still lower than that in the case group （P 〈0.01）; however, the insulin dosage and serum C-peptide were not significantly different between the two groups （P 〉0.05）. Moreover, the insulin dosage was not significant different from baseline to follow-up period in the case group. Conclusion AHST treatment showed no advantage in effectiveness in children with newly diagnosed type 1 diabetes, both in insulin dose and long term blood glucose control. Chin med J2014;（14）：2618-2622展开更多
Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach for...Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely unachievable.This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia.Moreover,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive agents.Mesenchymal stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection.In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.展开更多
The treatment of neurodegenerative diseases presents a growing need for innovation in relation to recent evidence in the field of reconstructive therapy using stem cells. Understanding the molecular mechanisms underly...The treatment of neurodegenerative diseases presents a growing need for innovation in relation to recent evidence in the field of reconstructive therapy using stem cells. Understanding the molecular mechanisms underlying neurodegenerative disorders, and the advent of methods able to induce neuronal stem cell differentiation allowed to develop innovative therapeutic approaches offering the prospect of healthy and perfectly functional cell transplants, able to replace the sick ones. Hence the importance of deepening the state of the art regarding the clinical applications of advanced cell therapy products for the regeneration of nerve tissue. Besides representing a promising area of tissue transplant surgery and a great achievement in the field of neurodegenerative disease, stem cell research presents certain critical issues that need to be carefully examined from the ethical perspective. In fact, a subject so complex and not entirely explored requires a detailed scientific and ethical evaluation aimed at avoiding improper and ineffective use, rather than incorrect indications, technical inadequacies, and incongruous expectations. In fact, the clinical usefulness of stem cells will only be certain if able to provide the patient with safe, long-term and substantially more effective strategies than any other treatment available.The present paper provides an ethical assessment of tissue regeneration through mesenchymal stem cells in neurodegenerative diseases with the aim to rule out the fundamental issues related to research and clinical translation.展开更多
The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments,often characterized by ...The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments,often characterized by high complexity from a surgical point of view,due to transplantation of multiple organs at the same time or at different times,and from an immunological point of view for stem cell therapy.The fundamental value in the field of organ transplants is,of course,a solidarity principle,namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery,or even of survival.The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems.The general principle of respect for human life,both of the donor and of the recipient,evokes the need not to put oneself and one’s neighbor in dangerous conditions.The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person,the respect due to the dead,the voluntary nature of the donation and the consent to the same,the gratuitousness of the donation,the scientific progress and the development of surgical techniques,and the policies of health promotion.展开更多
Ethical concerns about stem cell-based research have delayed important advances in many areas of medicine,including cardiology.The introduction of induced pluripotent stem cells(iPSCs)has supplanted the need to use hu...Ethical concerns about stem cell-based research have delayed important advances in many areas of medicine,including cardiology.The introduction of induced pluripotent stem cells(iPSCs)has supplanted the need to use human stem cells for most purposes,thus eliminating all ethical controversies.Since then,many new avenues have been opened in cardiology research,not only in approaches to tissue replacement but also in the design and testing of antiarrhythmic drugs.This methodology has advanced to the point where induced human cardiomyocyte cell lines can now also be obtained from commercial sources or tissue banks.Initial studies with readily available iPSCs have generally confirmed that their behavioral characteristics accurately predict the behavior of beating cardiomyocytes in vivo.As a result,iPSCs can provide new ways to study arrhythmias and heart disease in general,accelerating the development of new,more effective antiarrhythmic drugs,clinical diagnoses,and personalized medical care.The focus on producing cardiomyocytes that can be used to replace damaged heart tissue has somewhat diverted interest in a host of other applications.This manuscript is intended to provide non-specialists with a brief introduction and overview of the research carried out in the field of heart rhythm disorders.展开更多
AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in vivo.METH...AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in vivo.METHODS：MSCs were infected by lentivirus constructed with CXCR4.The expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain reaction.CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic activities.CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR.The histological structure of DR in rats was inspected by hematoxylin and eosin staining.The expression of rhodopsin,neuron-specific enolase（NSE）,and inflammatory cytokines interleukin（IL）-6 and tumor necrosis factor（TNF）-α was examined by Western blot and immunohistochemical analyses.RESULTS：The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and protein.Improved migration activities were observed in CXCR4-overexpressing MSCs.Further,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo.CONCLUSION：The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of DR.CXCR4-overexpressing MSCs can be a novel strategy for treating DR.展开更多
Objective: The local regulations for conducting experimental and clinical cell therapy studies are dependent on the national and cultural approach to the issue, and may have many common aspects as well as differences ...Objective: The local regulations for conducting experimental and clinical cell therapy studies are dependent on the national and cultural approach to the issue, and may have many common aspects as well as differences with the regulations in other countries.The study reflects the latest national aspects of cell therapy in Iran and relevant regulations. Methods: The following topics are discussed in the article including sources of cell harvest, regulations for cell disposal, stem cell manufacturing, and economic aspects of stem cell, based on current practice in Iran. Results: All cell therapy trials in Iran are required to strictly abide with the ethical codes, national and local regulations, and safety requirements, as well as considering human rights and respect. Adherence to these standards has facilitated the conduct of human cell therapy trials for research, academic advancement, and therapy. Conclusions: The cell therapy trials based on the aforementioned regulations may be assumed to be ethical and they are candidates for clinical translations based on safety and efficacy issues.展开更多
BACKGROUND: The transplantation of limbal epithelial cells cultivated on amniotic membrane is a newly developed treatment for limbal stem cell deficiency. The purpose of our study was to investigate the biological cha...BACKGROUND: The transplantation of limbal epithelial cells cultivated on amniotic membrane is a newly developed treatment for limbal stem cell deficiency. The purpose of our study was to investigate the biological characteristics of limbal epithelial cells and evaluate the effect of transplantation of cultivated human limbal epithelial cells on ocular surface reconstruction in limbal stem cell deficiency rat model. METHODS: Human limbal cells were isolated and cultivated in vitro. Cytokeratins 3, 12, and 19 (K3, K12 and K19) and p63 were detected by immunofluorescent staining or RT-PCR. BrdU labelling test was used to identify the slow cycling cells in the cultures. Limbal stem cell deficiency was established in rat cornea by alkali burn. Two weeks after injury, the rats received transplants of human limbal stem cells cultivated on amniotic membrane carrier. The therapeutic effect was evaluated by slit lamp observation, Hemotoxin and Eosin (HE) staining and immunofluorescent staining. RESULTS: On day 7 in primary culture, p63 and K19 were strongly expressed by most cells but only a few cells expressed K3. On days 14 and 21, p63 and K19 were still expressed by a majority of cells, but the expressive intensity of p63 decreased in a number of cells, while the proportion of K3 positive cells increased slightly and some cells coexpressed p63 and K3. RT-PCR showed that gene expression of both p63 and K12 were positive in cultivated limbal cells, but in mature superficial epithelial cells, only K12 was detected. BrdU labelling test showed that most cells were labelled with BrdU after 7 days' labelling and BrdU label retaining cells were observed after chasing for 21 days with BrdU free medium. For in vivo test, slit lamp observation, HE staining and immunofluorescent staining showed that the rats receiving transplant of human limbal stem cells cultivated on amniotic membrane grew reconstructed corneas with intact epithelium, improved transparency and slight or no neovascularization. A majority of epithelial cells of the reconstructed cornea were positive to antihuman nuclear antibody and cells expressing K3 were found mainly in superfacial epithelium. CONCLUSIONS: Limbal stem cells can be cultivated in vitro: the cells are characterized by high proliferation and slow cycling and identified as p63/K19 positive and K3/K12 negative. During culture, some stem cells can proliferate and differentiate into mature cornea epithelial cells. Amniotic membrane is a suitable carrier for limbal stem cells. Transplantation of human limbal stem cells cultivated on amniotic membrane can functionally reconstruct rat cornea with limbal stem cell deficiency.展开更多
Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr...Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr virus and are prevalent in East Asia and Latin America.Except for that of limited-stage ENKL,the prognosis of both diseases was poor in the previous decade.The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis,but there is still room for further treatment progress.Recently,the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients.This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients.Due to the rarity of the disease,a standard treatment for ANKL remains to be established.Currently,allogeneic stem cell transplantation is the only curative treatment,and this is even applicable to chemo-resistant ANKL patients.In this review,we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.展开更多
文摘Crohn's disease(CD)is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract.The etiology of CD is unknown;however,genetic,epigenetic,environmental,and lifestyle factors could play an essential role in the onset and establishment of the disease.CD results from immune dysregulation due to loss of the healthy symbiotic relationship between host and intestinal flora and or its antigens.It affects both sexes equally with a male to female ratio of 1.0,and its onset can occur at any age,but the diagnosis is most commonly observed in the range of 20 to 40 years of age.CD diminishes quality of life,interferes with social activities,traumatizes due to the stigma of incontinence,fistulae,strictures,and colostomies,and in severe cases,affects survival when compared to the general population.Symptoms fluctuate between periods of remission and activity in which complications such as fistulas,strictures,and the need for bowel resection,surgery,and colostomy implantation make up the most severe aspects of the disease.CD can be progressive and the complications recurrent despite treatment with anti-inflammatory drugs,corticosteroids,immunosuppressants,and biological agents.However,over time many patients become refractory without treatment alternatives,and in this scenario,hematopoietic stem cell transplantation(HSCT)has emerged as a potential treatment option.The rationale for the use of HSCT for CD is anchored in animal studies and human clinical trials where HSCT could reset a patient's immune system by eliminating disease-causing effector cells and upon immune recovery increase regulatory and suppressive immune cells.Autologous HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without CD34+selection has been to date the most common transplant conditioning regimen adopted.In this review we will address the current situation regarding CD treatment with HSCT and emphasize the medical,ethical,and legal aspects that permeate the procedure in Brazil.
文摘It is well known that to achieve an acceptable engraftment and survival in stem cell therapy, an human leukocyte antigens(HLA) identical stem cell transplant is strongly required. However, the availability of the HLA matched donors even among family members is extremely limited, so preimplantation HLA typing provides an attractive practical tool of stem cell therapy for children requiring HLA matched stem cell transplantation. The present experience of preimplantation genetic diagnosis(PGD) for HLA typing of over one thousand cases shows that PGD provides the at-risk couples with the option to establish an unaffected pregnancy, which may benefit the affected member of the family with hemoglobinopathies, immunodeficiencies and other congenital or acquired bone marrow failures. Despite ethical issues involved in preimplantation HLA typing, the data presented below show an extremely high attractiveness of this option for the couples with affected children requiring HLA compatible stem cell transplantation.
基金Shenzhen Science and Technology Innovation Committee Projects,No.JCYJ20170816105416349Shenzhen High-Level Hospital Construction Fund,Shenzhen Key Medical Discipline Construction Fund,No.SZXK010.
文摘BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.
文摘Background It has been indicated that autologous hematopoietic stem cell transplantation （AHST） is a promising treatment to adults with type 1 diabetes, however, the application of AHST therapy to children with type 1 diabetes still needs more data. The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes. Methods This 1：2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology, Beijing Children＇s Hospital from 2009-2010. The case group included 14 patients, who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010. The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization. We compared the baseline and follow-up data of them, including ketoacidosis onset, clinical variables （glycosylated hemoglobin （HbAlc）, insulin dosage and serum C-peptide）. Results The clinical characteristics of the patients was comparable between the case group and the control group. At 6-12 months （（10.7±4.2） months） after AHST treatment, we found 11 patients in the case group did not stop the insulin therapy, three cases stopped insulin treatment for 2, 3 and 11 months, respectively. No diabetic ketoacidosis （DKA） occurred after transplantation in all the patients in the case group. HbAlc in the control group was significant lower than that in the case group （P 〈0.01）, while the insulin dosage and serum C-peptide were not significant different between the two groups （P 〉0.05）. In order to eliminate the honeymoon effect, we performed final follow-up at the 3-5 years （（4.2±1.8） years） after AHST treatment, and found that HbAlc in the control group was still lower than that in the case group （P 〈0.01）; however, the insulin dosage and serum C-peptide were not significantly different between the two groups （P 〉0.05）. Moreover, the insulin dosage was not significant different from baseline to follow-up period in the case group. Conclusion AHST treatment showed no advantage in effectiveness in children with newly diagnosed type 1 diabetes, both in insulin dose and long term blood glucose control. Chin med J2014;（14）：2618-2622
文摘Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely unachievable.This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia.Moreover,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive agents.Mesenchymal stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection.In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.
文摘The treatment of neurodegenerative diseases presents a growing need for innovation in relation to recent evidence in the field of reconstructive therapy using stem cells. Understanding the molecular mechanisms underlying neurodegenerative disorders, and the advent of methods able to induce neuronal stem cell differentiation allowed to develop innovative therapeutic approaches offering the prospect of healthy and perfectly functional cell transplants, able to replace the sick ones. Hence the importance of deepening the state of the art regarding the clinical applications of advanced cell therapy products for the regeneration of nerve tissue. Besides representing a promising area of tissue transplant surgery and a great achievement in the field of neurodegenerative disease, stem cell research presents certain critical issues that need to be carefully examined from the ethical perspective. In fact, a subject so complex and not entirely explored requires a detailed scientific and ethical evaluation aimed at avoiding improper and ineffective use, rather than incorrect indications, technical inadequacies, and incongruous expectations. In fact, the clinical usefulness of stem cells will only be certain if able to provide the patient with safe, long-term and substantially more effective strategies than any other treatment available.The present paper provides an ethical assessment of tissue regeneration through mesenchymal stem cells in neurodegenerative diseases with the aim to rule out the fundamental issues related to research and clinical translation.
文摘The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments,often characterized by high complexity from a surgical point of view,due to transplantation of multiple organs at the same time or at different times,and from an immunological point of view for stem cell therapy.The fundamental value in the field of organ transplants is,of course,a solidarity principle,namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery,or even of survival.The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems.The general principle of respect for human life,both of the donor and of the recipient,evokes the need not to put oneself and one’s neighbor in dangerous conditions.The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person,the respect due to the dead,the voluntary nature of the donation and the consent to the same,the gratuitousness of the donation,the scientific progress and the development of surgical techniques,and the policies of health promotion.
文摘Ethical concerns about stem cell-based research have delayed important advances in many areas of medicine,including cardiology.The introduction of induced pluripotent stem cells(iPSCs)has supplanted the need to use human stem cells for most purposes,thus eliminating all ethical controversies.Since then,many new avenues have been opened in cardiology research,not only in approaches to tissue replacement but also in the design and testing of antiarrhythmic drugs.This methodology has advanced to the point where induced human cardiomyocyte cell lines can now also be obtained from commercial sources or tissue banks.Initial studies with readily available iPSCs have generally confirmed that their behavioral characteristics accurately predict the behavior of beating cardiomyocytes in vivo.As a result,iPSCs can provide new ways to study arrhythmias and heart disease in general,accelerating the development of new,more effective antiarrhythmic drugs,clinical diagnoses,and personalized medical care.The focus on producing cardiomyocytes that can be used to replace damaged heart tissue has somewhat diverted interest in a host of other applications.This manuscript is intended to provide non-specialists with a brief introduction and overview of the research carried out in the field of heart rhythm disorders.
基金Supported by the National Natural Science Foundation of China(No.81700846)Tianjin Science and Technology Project of China(No.13ZCZDSY01500)
文摘AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in vivo.METHODS：MSCs were infected by lentivirus constructed with CXCR4.The expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain reaction.CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic activities.CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR.The histological structure of DR in rats was inspected by hematoxylin and eosin staining.The expression of rhodopsin,neuron-specific enolase（NSE）,and inflammatory cytokines interleukin（IL）-6 and tumor necrosis factor（TNF）-α was examined by Western blot and immunohistochemical analyses.RESULTS：The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and protein.Improved migration activities were observed in CXCR4-overexpressing MSCs.Further,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo.CONCLUSION：The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of DR.CXCR4-overexpressing MSCs can be a novel strategy for treating DR.
文摘Objective: The local regulations for conducting experimental and clinical cell therapy studies are dependent on the national and cultural approach to the issue, and may have many common aspects as well as differences with the regulations in other countries.The study reflects the latest national aspects of cell therapy in Iran and relevant regulations. Methods: The following topics are discussed in the article including sources of cell harvest, regulations for cell disposal, stem cell manufacturing, and economic aspects of stem cell, based on current practice in Iran. Results: All cell therapy trials in Iran are required to strictly abide with the ethical codes, national and local regulations, and safety requirements, as well as considering human rights and respect. Adherence to these standards has facilitated the conduct of human cell therapy trials for research, academic advancement, and therapy. Conclusions: The cell therapy trials based on the aforementioned regulations may be assumed to be ethical and they are candidates for clinical translations based on safety and efficacy issues.
文摘BACKGROUND: The transplantation of limbal epithelial cells cultivated on amniotic membrane is a newly developed treatment for limbal stem cell deficiency. The purpose of our study was to investigate the biological characteristics of limbal epithelial cells and evaluate the effect of transplantation of cultivated human limbal epithelial cells on ocular surface reconstruction in limbal stem cell deficiency rat model. METHODS: Human limbal cells were isolated and cultivated in vitro. Cytokeratins 3, 12, and 19 (K3, K12 and K19) and p63 were detected by immunofluorescent staining or RT-PCR. BrdU labelling test was used to identify the slow cycling cells in the cultures. Limbal stem cell deficiency was established in rat cornea by alkali burn. Two weeks after injury, the rats received transplants of human limbal stem cells cultivated on amniotic membrane carrier. The therapeutic effect was evaluated by slit lamp observation, Hemotoxin and Eosin (HE) staining and immunofluorescent staining. RESULTS: On day 7 in primary culture, p63 and K19 were strongly expressed by most cells but only a few cells expressed K3. On days 14 and 21, p63 and K19 were still expressed by a majority of cells, but the expressive intensity of p63 decreased in a number of cells, while the proportion of K3 positive cells increased slightly and some cells coexpressed p63 and K3. RT-PCR showed that gene expression of both p63 and K12 were positive in cultivated limbal cells, but in mature superficial epithelial cells, only K12 was detected. BrdU labelling test showed that most cells were labelled with BrdU after 7 days' labelling and BrdU label retaining cells were observed after chasing for 21 days with BrdU free medium. For in vivo test, slit lamp observation, HE staining and immunofluorescent staining showed that the rats receiving transplant of human limbal stem cells cultivated on amniotic membrane grew reconstructed corneas with intact epithelium, improved transparency and slight or no neovascularization. A majority of epithelial cells of the reconstructed cornea were positive to antihuman nuclear antibody and cells expressing K3 were found mainly in superfacial epithelium. CONCLUSIONS: Limbal stem cells can be cultivated in vitro: the cells are characterized by high proliferation and slow cycling and identified as p63/K19 positive and K3/K12 negative. During culture, some stem cells can proliferate and differentiate into mature cornea epithelial cells. Amniotic membrane is a suitable carrier for limbal stem cells. Transplantation of human limbal stem cells cultivated on amniotic membrane can functionally reconstruct rat cornea with limbal stem cell deficiency.
文摘Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr virus and are prevalent in East Asia and Latin America.Except for that of limited-stage ENKL,the prognosis of both diseases was poor in the previous decade.The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis,but there is still room for further treatment progress.Recently,the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients.This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients.Due to the rarity of the disease,a standard treatment for ANKL remains to be established.Currently,allogeneic stem cell transplantation is the only curative treatment,and this is even applicable to chemo-resistant ANKL patients.In this review,we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.
