Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2020, Vol. 11 Issue (1) : 141-153     DOI: 10.14336/AD.2019.0421
Review Article |
The Clinical Efficacy and Safety of Stem Cell Therapy for Diabetes Mellitus: A Systematic Review and Meta-Analysis
Yazhen Zhang1,2, Wenyi Chen1,2, Bing Feng1,2, Hongcui Cao1,2,*
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
Download: PDF(1602 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Diabetes mellitus (DM) is a chronic metabolic disease with high morbidity and mortality. Recently, stem cell-based therapy for DM has shown considerable promise. Here, we undertook a systematic review and meta-analysis of published clinical studies to evaluate the efficacy and safety of stem cell therapy for both type 1 DM (T1DM) and type 2 DM (T2DM). The PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and ClinicalTrials.gov databases were searched up to November 2018. We employed a fixed-effect model using 95% confidence intervals (CIs) when no statistically significant heterogeneity existed. Otherwise, a random-effects statistical model was used. Twenty-one studies met our inclusion criteria: ten T1DM studies including 226 patients and eleven T2DM studies including 386 patients. Stem cell therapy improved C-peptide levels (mean difference (MD), 0.41; 95% CI, 0.06 to 0.76) and glycosylated hemoglobin (HbA1c; MD, -3.46; 95% CI, -6.01 to -0.91) for T1DM patients. For T2DM patients, stem cell therapy improved C-peptide levels (MD, 0.33; 95% CI, 0.07 to 0.59), HbA1c (MD, -0.87; 95% CI, -1.37 to -0.37) and insulin requirements (MD, -35.76; 95% CI, -40.47 to -31.04). However, there was no significant change in fasting plasma glucose levels (MD, -0.52; 95% CI, -1.38 to 0.34). Subgroup analyses showed significant HbA1c and C-peptide improvements in patients with T1DM treated with bone marrow hematopoietic stem cells (BM-HSCs), while there was no significant change in the mesenchymal stem cell (MSC) group. In T2DM, HbA1c and insulin requirements decreased significantly after MSC transplantation, and insulin requirements and C-peptide levels were significantly improved after bone marrow mononuclear cell (BM-MNC) treatment. Stem cell therapy is a relatively safe and effective method for selected individuals with DM. The data showed that BM-HSCs are superior to MSCs in the treatment of T1DM. In T2DM, MSC and BM-MNC transplantation showed favorable therapeutic effects.

Keywords diabetes mellitus      stem cells      cell therapy      meta-analysis      regenerative medicine      systematic review     
Corresponding Authors: Hongcui Cao   
About author:

These authors contributed equally to this work.

Just Accepted Date: 10 May 2019   Issue Date: 15 January 2020
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Yazhen Zhang
Wenyi Chen
Bing Feng
Hongcui Cao
Cite this article:   
Yazhen Zhang,Wenyi Chen,Bing Feng, et al. The Clinical Efficacy and Safety of Stem Cell Therapy for Diabetes Mellitus: A Systematic Review and Meta-Analysis[J]. Aging and disease, 2020, 11(1): 141-153.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2019.0421     OR     http://www.aginganddisease.org/EN/Y2020/V11/I1/141
Figure 1.  Flow chart of the selection process for this meta-analysis.
Figure 2.  Forest plot of C-peptide levels in type 1 diabetes mellitus (T1DM). Comparison of C-peptide levels in T1DM individuals between baseline and 12 months after stem cell therapy. A random-effects meta-analysis model (Mantel-Haenszel method) was used in this analysis. Each trial is represented by a square, the center of which denotes the mean difference (MD) for that trial. The size of the square is proportional to the information in that trial. The ends of the horizontal bars denote a 95% confidence interval. The black diamond gives the overall MD for all trials combined.
Author and yearCountrySample size (cell therapy/ control)Male (%) (cell therapy/control)Mean age (cell therapy/control) (years)History of DMRegimenRegimens (cell number) doseInjection modeMean follow-up period
Ye 2017 [25]China8/10(T1DM)37.5% /40%18.86 /20.18<6 mBM-HSCNAIV12 m
D'Addio 2014 [18]Poland65(T1DM)63%20.4<12 mBM-HSC5.8 ×l06 /kgIV48 m
Zhang 2012 [26]China9(T1DM)55.6%17.62 yBM-HSC12.31 ×l06 /kgIV12 m
Li 2012 [39]China13(T1DM)69.2%14.1<12 mBM-HSC4 ×l06 /kgIV42 m
Gu 2012 [44]China28(T1DM)50%17.63 mBM-HSCNAIV19.3 m
Snarski 2010 [24]Poland8(T1DM)50%25.82 mBM-HSC4.14×l06 /kgIV7 m
Couri 2009 [28]Brazil23(T1DM)73.9%18.4<2 mBM-HSC10.52×l06 /kgIV29.8 m
Voltarelli 2007 [16]Brazil15(T1DM)73.3%19.2<2 mBM-HSC11 ×l06 /kgIV18.8 m
Carlsson 2014 [27]Sweden9/9(T1DM)88.9% /55.6%24 /27<3 wMSC2.75 ×l06 /kgIV12 m
Hu 2013 [36]China15/14(T1DM)60% /57.1%17.6 /18.2New onsetMSC2.6 ×107/kgIV21 m
Bhansali 2017 [23]India10/10(T2DM)80% /60%50.5 /53.514.5 yMSC1 ×l06 /kgSuperior pancreatico-duodenal artery12 m
Hu 2016 [34]China31/30(T2DM)54.8% /53.3%52.43 /53.218.95 /8.3 yMSC6.1 ×107IV36 m
Skyler 2015 [47]USA45/16(T2DM)62.2% /75%56.7 /58.710.1yMSC1.1×106/kgIV12 w
Guan 2015 [48]China6(T2DM)100%40.542.7 wMSC0.88×106/kgIV33.2 m
Liu 2014 [30]China22(T2DM)68.18%52.98.7 yMSC1×106/kgIV on Day 5+ Splenic artery on Day 1012 m
Jiang 2011 [29]China10(T2DM)70%6611 yMSC1.35 ×106IV6 m
Bhansali 2017 [33]India7(T2DM)85.7%4615 yBM-MNC1.2 ×109Superior pancreatico-duodenal artery6 m
Bhansali 2017 [23]India10/10(T2DM)70% /60%44.5 /53.513.5 yBM-MNC1 ×109Superior pancreatico-duodenal artery12 m
Wu 2014 [32]China20/20(T2DM)60% /55.5%56.4 /54.99.7 yBM-MNC4.01×109Dorsal pancreatic artery12 m
Bhansali 2014 [31]India11/10(T2DM)81.8% /70%51 /5415.8 yBM-MNC2.9 ×108Superior pancreatico-duodenal artery12 m
Hu 2012 [35]China56/62(T2DM)67.8% /58%50.4 /50.28.6 yBM-MNC2.8 ×109Dorsal pancreatic artery33 m
Bhansali 2009 [17]India10(T2DM)80%57.514.6 yBM-MNC3.5 × 108Superior pancreatico-duodenal artery6 m
Table 1  Characteristics of the included studies.
Figure 3.  Forest plot for glycosylated hemoglobin (HbA1c) in T1DM. Comparison of HbA1c levels in T1DM individuals between baseline and 12 months after stem cell therapy. A random-effects meta-analysis model (Mantel-Haenszel method) was used in this analysis.
Figure 4.  Forest plot of C-peptide levels in type 2 diabetes mellitus (T2DM). Comparison of C-peptide levels in T2DM individuals between baseline and 12 months after stem cell therapy. A random-effects meta-analysis model (Mantel-Haenszel method) was used in this analysis.
Figure 5.  Forest plot of HbA1c in T2DM. Comparison of HbA1c levels in T2DM individuals between baseline and 12 months after stem cell therapy. A random-effects meta-analysis model (Mantel-Haenszel method) was used in this analysis.
Figure 6.  Forest plot of insulin requirement in T2DM. Comparison of insulin requirement in T2DM individuals between baseline and 12 months after stem cell therapy. A fixed-effects meta-analysis model (Mantel-Haenszel method) was used in this analysis.
Figure 7.  Forest plot of fasting plasma glucose (FPG) in T2DM. Comparison of FPG levels in T2DM individuals between baseline and 12 months after stem cell therapy. A random-effects meta-analysis model (Mantel-Haenszel method) was used in this analysis.
[1] International Diabetes Federation.IDF Diabetes Atlas 8th edn. Brussels, Belgium: International Diabetes Federation, 2017.
[2] American Diabetes Association (2004). Diagnosis and classification of diabetes mellitus. Diabetes Care, 27 Suppl 1:S5-s10.
[3] Kolb H, Mandrup-Poulsen T (2005). An immune origin of type 2 diabetes? Diabetologia, 48:1038-1050.
[4] Todd JA (2010). Etiology of type 1 diabetes. Immunity, 32:457-467.
[5] Melendez-Ramirez LY, Richards RJ, Cefalu WT (2010). Complications of type 1 diabetes. Endocrinol Metab Clin North Am, 39:625-640.
[6] Das Evcimen N, King G (2007). The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol. Res., 55:498-510.
[7] Peng BY, Dubey NK, Mishra VK, Tsai FC, Dubey R, Deng WP, et al. (2018). Addressing Stem Cell Therapeutic Approaches in Pathobiology of Diabetes and Its Complications. J Diabetes Res, 2018:7806435.
[8] Lilly MA, Davis MF, Fabie JE, Terhune EB, Gallicano GI (2016). Current stem cell based therapies in diabetes. Am J Stem Cells, 5:87-98.
[9] Teramura Y, Iwata H (2010). Bioartificial pancreas microencapsulation and conformal coating of islet of Langerhans. Adv Drug Deliv Rev, 62:827-840.
[10] Gaba RC, Garcia-Roca R, Oberholzer J (2012). Pancreatic islet cell transplantation: an update for interventional radiologists. J Vasc Interv Radiol, 23:583-594; quiz 594.
[11] Robertson RP (2004). Islet transplantation as a treatment for diabetes - a work in progress. N Engl J Med, 350:694-705.
[12] Gibly RF, Graham JG, Luo X, Lowe WLJr, Hering BJ, Shea LD (2011). Advancing islet transplantation: from engraftment to the immune response. Diabetologia, 54:2494-2505.
[13] Chhabra P, Brayman KL (2013). Stem cell therapy to cure type 1 diabetes: from hype to hope. Stem Cells Transl Med, 2:328-336.
[14] Hess D, Li L, Martin M, Sakano S, Hill D, Strutt B, et al. (2003). Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol, 21:763-770.
[15] Pera MF, Tam PP (2010). Extrinsic regulation of pluripotent stem cells. Nature, 465:713-720.
[16] Voltarelli JC, Couri CEB, Stracieri ABPL, Oliveira MC, Moraes DA, Pieroni F, et al. (2007). Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. Journal of the American Medical Association, 297:1568-1576.
[17] Bhansali A, Upreti V, Khandelwal N, Marwaha N, Gupta V, Sachdeva N, et al. (2009). Efficacy of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cells Dev, 18:1407-1416.
[18] D'Addio F, Valderrama Vasquez A, Ben Nasr M, Franek E, Zhu D, Li L, et al. (2014). Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset type 1 diabetes: a multicenter analysis. Diabetes, 63:3041-3046.
[19] Rahim F, Arjmand B, Shirbandi K, Payab M, Larijani B (2018). Stem cell therapy for patients with diabetes: a systematic review and meta-analysis of metabolomics-based risks and benefits. Stem Cell Investig, 5:40.
[20] El-Badawy A, El-Badri N (2016). Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis. PLoS One, 11:e0151938.
[21] Moher D, Liberati A, Tetzlaff J, Altman DG (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol, 62:1006-1012.
[22] Downs SH, Black N (1998). The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health, 52:377-384.
[23] Bhansali S, Dutta P, Kumar V, Yadav MK, Jain A, Mudaliar S, et al. (2017). Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study. Stem Cells Dev, 26:471-481.
[24] Snarski E, Milczarczyk A, Torosian T, Paluszewska M, Urbanowska E, Krol M, et al. (2011). Independence of exogenous insulin following immunoablation and stem cell reconstitution in newly diagnosed diabetes type I. Bone Marrow Transplant, 46:562-566.
[25] Ye L, Li L, Wan B, Yang M, Hong J, Gu W, et al. (2017). Immune response after autologous hematopoietic stem cell transplantation in type 1 diabetes mellitus. Stem Cell Res Ther, 8:90.
[26] Zhang X, Ye L, Hu J, Tang W, Liu R, Yang M, et al. (2012). Acute response of peripheral blood cell to autologous hematopoietic stem cell transplantation in type 1 diabetic patient. PLoS One, 7:e31887.
[27] Carlsson PO, Schwarcz E, Korsgren O, Le Blanc K (2015). Preserved beta-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes, 64:587-592.
[28] Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, et al. (2009). C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. Jama, 301:1573-1579.
[29] Jiang R, Han Z, Zhuo G, Qu X, Li X, Wang X, et al. (2011). Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med, 5:94-100.
[30] Liu X, Zheng P, Wang X, Dai G, Cheng H, Zhang Z, et al. (2014). A preliminary evaluation of efficacy and safety of Wharton's jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cell Res Ther, 5:57.
[31] Bhansali A, Asokumar P, Walia R, Bhansali S, Gupta V, Jain A, et al. (2014). Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: a randomized placebo-controlled study. Cell Transplant, 23:1075-1085.
[32] Wu Z, Cai J, Chen J, Huang L, Wu W, Luo F, et al. (2014). Autologous bone marrow mononuclear cell infusion and hyperbaric oxygen therapy in type 2 diabetes mellitus: an open-label, randomized controlled clinical trial. Cytotherapy, 16:258-265.
[33] Bhansali S, Dutta P, Yadav MK, Jain A, Mudaliar S, Hawkins M, et al. (2017). Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on beta-cell function and insulin sensitivity. Diabetol Metab Syndr, 9:50.
[34] Hu J, Wang Y, Gong H, Yu C, Guo C, Wang F, et al. (2016). Long term effect and safety of Wharton's jelly-derived mesenchymal stem cells on type 2 diabetes. Exp Ther Med, 12:1857-1866.
[35] Hu J, Li C, Wang L, Zhang X, Zhang M, Gao H, et al. (2012). Long term effects of the implantation of autologous bone marrow mononuclear cells for type 2 diabetes mellitus. Endocr J, 59:1031-1039.
[36] Hu J, Yu X, Wang Z, Wang F, Wang L, Gao H, et al. (2013). Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocr J, 60:347-357.
[37] Azab NI, AlKholy AF, Salem RF, Gabr H, ElAbd AM (2011). Comparison between bone marrow derived mesenchymal stem cells and hematopoietic stem cells in β-Islet transdifferentiation. Stem Cells:2(1):1-10.
[38] Arany EJ, Waseem M, Strutt BJ, Chamson-Reig A, Bernardo A, Eng E, et al. (2018). Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice. Islets, 10:137-150.
[39] Li L, Shen S, Ouyang J, Hu Y, Hu L, Cui W, et al. (2012). Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves β-cell function in Chinese patients with new onset of type 1 diabetes. Journal of Clinical Endocrinology and Metabolism, 97:1729-1736.
[40] English K, Ryan JM, Tobin L, Murphy MJ, Barry FP, Mahon BP (2009). Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25(High) forkhead box P3+ regulatory T cells. Clin Exp Immunol, 156:149-160.
[41] Thakkar UG, Trivedi HL, Vanikar AV, Dave SD (2015). Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow-derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus. Cytotherapy, 17:940-947.
[42] Volarevic V, Al-Qahtani A, Arsenijevic N, Pajovic S, Lukic ML (2010). Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis. Autoimmunity, 43:255-263.
[43] Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH (2008). Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes, 57:1759-1767.
[44] Gu W, Hu J, Wang W, Li L, Tang W, Sun S, et al. (2012). Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes. Diabetes Care, 35:1413-1419.
[45] Burt RK, Slavin S, Burns WH, Marmont AM (2002). Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure? Blood, 99:768-784.
[46] Au WY, Lie AK, Kung AW, Liang R, Hawkins BR, Kwong YL (2005). Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation. Bone Marrow Transplant, 35:383-388.
[47] Skyler JS, Fonseca VA, Segal KR, Rosenstock J (2015). Allogeneic Mesenchymal Precursor Cells in Type 2 Diabetes: A Randomized, Placebo-Controlled, Dose-Escalation Safety and Tolerability Pilot Study. Diabetes Care, 38:1742-1749.
[48] Guan LX, Guan H, Li HB, Ren CA, Liu L, Chu JJ, et al. (2015). Therapeutic efficacy of umbilical cord-derived mesenchymal stem cells in patients with type 2 diabetes. Exp Ther Med, 9:1623-1630.
[49] Phadnis SM, Joglekar MV, Dalvi MP, Muthyala S, Nair PD, Ghaskadbi SM, et al. (2011). Human bone marrow-derived mesenchymal cells differentiate and mature into endocrine pancreatic lineage in vivo. Cytotherapy, 13:279-293.
[50] Carlotti F, Zaldumbide A, Loomans CJ, van Rossenberg E, Engelse M, de Koning EJ, et al. (2010). Isolated human islets contain a distinct population of mesenchymal stem cells. Islets, 2:164-173.
[51] Phuc PV, Nhung TH, Loan DT, Chung DC, Ngoc PK (2011). Differentiating of banked human umbilical cord blood-derived mesenchymal stem cells into insulin-secreting cells. In Vitro Cell Dev Biol Anim, 47:54-63.
[52] Liao W, Xie J, Zhong J, Liu Y, Du L, Zhou B, et al. (2009). Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation, 87:350-359.
[53] Si Y, Zhao Y, Hao H, Liu J, Guo Y, Mu Y, et al. (2012). Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes, 61:1616-1625.
[54] Dong QY, Chen L, Gao GQ, Wang L, Song J, Chen B, et al. (2008). Allogeneic diabetic mesenchymal stem cells transplantation in streptozotocin-induced diabetic rat. Clin Invest Med, 31:E328-337.
[55] Park KS, Kim YS, Kim JH, Choi B, Kim SH, Tan AH, et al. (2010). Trophic molecules derived from human mesenchymal stem cells enhance survival, function, and angiogenesis of isolated islets after transplantation. Transplantation, 89:509-517.
[56] Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, et al. (2006). Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci U S A, 103:17438-17443.
[57] Welsh N, Cnop M, Kharroubi I, Bugliani M, Lupi R, Marchetti P, et al. (2005). Is there a role for locally produced interleukin-1 in the deleterious effects of high glucose or the type 2 diabetes milieu to human pancreatic islets? Diabetes, 54:3238-3244.
[58] Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab, 280:E745-751.
[1] Supplementary data Download
[1] Shijin Xia, Changxi Zhou, Bill Kalionis, Xiaoping Shuang, Haiyan Ge, Wen Gao. Combined Antioxidant, Anti-inflammaging and Mesenchymal Stem Cell Treatment: A Possible Therapeutic Direction in Elderly Patients with Chronic Obstructive Pulmonary Disease[J]. Aging and disease, 2020, 11(1): 129-140.
[2] Zhongfeng Liu, Xuan Wang, Kewen Jiang, Xunming Ji, Y. Alex Zhang, Zhiguo Chen. TNFα-induced Up-regulation of Ascl2 Affects the Differentiation and Proliferation of Neural Stem Cells[J]. Aging and disease, 2019, 10(6): 1207-1220.
[3] Chia-Ter Chao, Jui Wang, Jenq-Wen Huang, Ding-Cheng Chan, Kuo-Liong Chien. Frailty Predicts an Increased Risk of End-Stage Renal Disease with Risk Competition by Mortality among 165,461 Diabetic Kidney Disease Patients[J]. Aging and disease, 2019, 10(6): 1270-1281.
[4] Le Gao, Shuqing Yu, Andrea Cipriani, Shanshan Wu, Yi Huang, Zilu Zhang, Jun Yang, Yixin Sun, Zhirong Yang, Sanbao Chai, Yuan Zhang, Linong Ji, Siyan Zhan, Feng Sun. Neurological Manifestation of Incretin-Based Therapies in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis[J]. Aging and disease, 2019, 10(6): 1311-1319.
[5] Yuan Tan, Minjing Ke, Zhijian Huang, Cheong-Meng Chong, Xiaotong Cen, Jia-Hong Lu, Xiaoli Yao, Dajiang Qin, Huanxing Su. Hydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson’s Disease[J]. Aging and disease, 2019, 10(5): 1037-1048.
[6] Yoorim Choi, Dong Suk Yoon, Kyoung-Mi Lee, Seong Mi Choi, Myon-Hee Lee, Kwang Hwan Park, Seung Hwan Han, Jin Woo Lee. Enhancement of Mesenchymal Stem Cell-Driven Bone Regeneration by Resveratrol-Mediated SOX2 Regulation[J]. Aging and disease, 2019, 10(4): 818-833.
[7] Linsha Ma, Jingchao Hu, Yu Cao, Yilin Xie, Hua Wang, Zhipeng Fan, Chunmei Zhang, Jinsong Wang, Chu-Tse Wu, Songlin Wang. Maintained Properties of Aged Dental Pulp Stem Cells for Superior Periodontal Tissue Regeneration[J]. Aging and disease, 2019, 10(4): 793-806.
[8] Navneet Kumar Dubey, Hong-Jian Wei, Sung-Hsun Yu, David F. Williams, Joseph R. Wang, Yue-Hua Deng, Feng-Chou Tsai, Peter D. Wang, Win-Ping Deng. Adipose-derived Stem Cells Attenuates Diabetic Osteoarthritis via Inhibition of Glycation-mediated Inflammatory Cascade[J]. Aging and disease, 2019, 10(3): 483-496.
[9] Tseng Chin-Hsiao. Metformin and the Risk of Dementia in Type 2 Diabetes Patients[J]. Aging and disease, 2019, 10(1): 37-48.
[10] Hongling Li, Junfen Fan, Linyuan Fan, Tangping Li, Yanlei Yang, Haoying Xu, Luchan Deng, Jing Li, Tao Li, Xisheng Weng, Shihua Wang, Robert Chunhua Zhao. MiRNA-10b Reciprocally Stimulates Osteogenesis and Inhibits Adipogenesis Partly through the TGF-β/SMAD2 Signaling Pathway[J]. Aging and disease, 2018, 9(6): 1058-1073.
[11] Ashok K. Shetty, Maheedhar Kodali, Raghavendra Upadhya, Leelavathi N. Madhu. Emerging Anti-Aging Strategies - Scientific Basis and Efficacy[J]. Aging and disease, 2018, 9(6): 1165-1184.
[12] Changhong Ren, Hang Wu, Dongjie Li, Yong Yang, Yuan Gao, Yunneng Jizhang, Dachuan Liu, Xunming Ji, Xuxiang Zhang. Remote Ischemic Conditioning Protects Diabetic Retinopathy in Streptozotocin-induced Diabetic Rats via Anti-Inflammation and Antioxidation[J]. Aging and disease, 2018, 9(6): 1122-1133.
[13] Xue Jiang, Li Jiarui, Liang Jiaming, Chen Shulin. The Prevalence of Mild Cognitive Impairment in China: A Systematic Review[J]. Aging and disease, 2018, 9(4): 706-715.
[14] Yang Yao-Chih, Tsai Cheng-Yen, Chen Chien-Lin, Kuo Chia-Hua, Hou Chien-Wen, Cheng Shi-Yann, Aneja Ritu, Huang Chih-Yang, Kuo Wei-Wen. Pkcδ Activation is Involved in ROS-Mediated Mitochondrial Dysfunction and Apoptosis in Cardiomyocytes Exposed to Advanced Glycation End Products (Ages)[J]. Aging and disease, 2018, 9(4): 647-663.
[15] Yan Tao, Venkat Poornima, Chopp Michael, Zacharek Alex, Yu Peng, Ning Ruizhuo, Qiao Xiaoxi, Kelley Mark R., Chen Jieli. APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats[J]. Aging and disease, 2018, 9(3): 453-466.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd