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Open Access Article

Journal of Cell and Molecular Biology Research. 2021; 1: (1) ; 33-41 ; DOI: 10.12208/j.ijcmbr.20210007.

Advances in basic research of induced pluripotent stem cells in prevention and treatment of chronic complications in diabetes mellitus.
诱导多能干细胞在糖尿病慢性并发症防治中基础研究进展

作者: 王婉乔, 李彦欣 *

上海交通大学医学院附属上海儿童医学中心,血液肿瘤科,国家卫生健康委员会儿童血液肿瘤重点实验室 上海

上海交通大学医学院附属上海儿童医学中心,血液肿瘤科, 国家卫生健康委员会儿童血液肿瘤重点实验室 上海

*通讯作者: 李彦欣,单位:上海交通大学医学院附属上海儿童医学中心,血液肿瘤科, 国家卫生健康委员会儿童血液肿瘤重点实验室 上海;

发布时间: 2021-10-20 总浏览量: 1645

摘要

近年来,再生医学和干细胞治疗技术发展迅速,利用诱导多能干细胞(induced pluripotent stem cells, iPSCs)技术,能够将已经分化成熟的体细胞逆转为早期未分化的多能干细胞,再经各种细胞因子处理诱导其定向分化为终末目的细胞,其过程类似于胚胎细胞的生长发育过程。将此技术运用于糖尿病视网膜病变、糖尿病心肌病变、糖尿病神经病变以及糖尿病肾病等糖尿病常见慢性并发症的防治研究,并逐渐探索适用于临床的方法,开始成为糖尿病干细胞治疗领域的一大研究热点。研究显示,此种干细胞疗法在细胞和实验动物水平获得了积极的结果,并开始探索应用于临床。因此,笔者拟就iPSCs在糖尿病慢性并发症应用方面的基础研究进展进行概括并提出展望。

关键词: 诱导多能干细胞;糖尿病;细胞治疗;糖尿病视网膜病变;糖尿病心肌病;糖尿病周围神经病变;糖尿病肾病

Abstract

In recent years, the rapid development of regenerative medicine and stem cell therapy techniques has enabled the reversal of mature somatic cells into early undifferentiated pluripotent stem cells byusing induced pluripotent stem cells (iPSCs).After treatment with various cytokines, the cells were induced to differentiate into terminal target cells, which was similar to the growth and development process of embryonic cells.Applying this technology to the prevention and treatment of diabetic retinopathy, diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy and other chronic complications of diabetes, and gradually exploring the method suitable for clinical use, has become a major research hotspot in the field of diabetic stem cell therapy.The stem cell therapy has shown positive results at the cell and laboratory animal levels, and is beginning to be explored for clinical use.Therefore,I intend to summarize the basic research progress ofiPSCs in the application of chronic complications in DM and put forward the prospect.

Key words: Induced Pluripotent Stemcells; Diabetes Mellitus; Diabetic Retinopathy; Diabetic Cardiomyopathy; Diabetic Peripheral Neuropathy; Diabetic Nephropathy

参考文献 References

[1] TAKAHASHI K, TANABE K, OHNUKI M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors[J]. Cell, 2007, 131(5): 861-872.

[2] EBRAHIMI M, FOROUZESH M, RAOUFI S, et al. Differentiation of human induced pluripotent stem cells into erythroid cells[J]. Stem Cell Res Ther, 2020, 11(1): 483.

[3] VELMURUGAN B K, BHARATHI PRIYA L, POORNIMA P, et al. Biomaterial aided differentiation and maturation of induced pluripotent stem cells[J]. J Cell Physiol, 2019, 234(6): 8443-8454.

[4] STEICHEN C, HANNOUN Z, LUCE E, et al. Genomic integrity of human induced pluripotent stem cells: Reprogramming, differentiation and applications[J]. World J Stem Cells, 2019, 11(10): 729-747.

[5] SHI Y, INOUE H, WU J C, et al. Induced pluripotent stem cell technology: a decade of progress[J]. Nat Rev Drug Discov, 2017, 16(2): 115-130.

[6] MATTAPALLY S, PAWLIK K M, FAST V G, et al. Human Leukocyte Antigen Class I and II Knockout Human Induced Pluripotent Stem Cell-Derived Cells: Universal Donor for Cell Therapy[J]. J Am Heart Assoc, 2018, 7(23): e010239.

[7] MILLMAN J R, PAGLIUCA F W. Autologous Pluripotent Stem Cell-Derived β-Like Cells for Diabetes Cellular Therapy[J]. Diabetes, 2017, 66(5): 1111-1120.

[8] ZHANG D, JIANG W, LIU M, et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells[J]. Cell Res, 2009, 19(4): 429-438.

[9] SALERO E, BLENKINSOP T A, CORNEO B, et al. Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives[J]. Cell Stem Cell, 2012, 10(1): 88-95.

[10] GOLESTANEH N, CHU Y, XIAO Y Y, et al. Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration[J]. Cell Death Dis, 2017, 8(1): e2537.

[11] BRANDL C. Generation of Functional Retinal Pigment Epithelium from Human Induced Pluripotent Stem Cells[J]. Methods Mol Biol, 2019, 1834: 87-94.

[12] JI S L, TANG S B. Differentiation of retinal ganglion cells from induced pluripotent stem cells: a review[J]. Int J Ophthalmol, 2019, 12(1): 152-160.

[13] ZHU J, REYNOLDS J, GARCIA T, et al. Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line[J]. Stem Cells Transl Med, 2018, 7(2): 210-219.

[14] SIMARA P, TESAROVA L, REHAKOVA D, et al. Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells[J]. Stem Cells Dev, 2018, 27(1): 10-22.

[15] KIAMEHR M, KLETTNER A, RICHERT E, et al. Compromised Barrier Function in Human Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells from Type 2 Diabetic Patients[J]. Int J Mol Sci, 2019, 20(15).

[16] HALLAM D, HILGEN G, DORGAU B, et al. Human-Induced Pluripotent Stem Cells Generate Light Responsive Retinal Organoids with Variable and Nutrient-Dependent Efficiency[J]. Stem Cells, 2018, 36(10): 1535-1551.

[17] BARNEA-CRAMER A O, WANG W, LU S J, et al. Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice[J]. Sci Rep, 2016, 6: 29784.

[18] MANDAI M, FUJII M, HASHIGUCHI T, et al. iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice[J]. Stem Cell Reports, 2017, 8(1): 69-83.

[19] KAMAO H, MANDAI M, OHASHI W, et al. Evaluation of the Surgical Device and Procedure for Extracellular Matrix-Scaffold-Supported Human iPSC-Derived Retinal Pigment Epithelium Cell Sheet Transplantation[J]. Invest Ophthalmol Vis Sci, 2017, 58(1): 211-220.

[20] MANDAI M, WATANABE A, KURIMOTO Y, et al. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration[J]. N Engl J Med, 2017, 376(11): 1038-1046.

[21] ZHU J, CIFUENTES H, REYNOLDS J, et al. Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina[J]. Cell Stem Cell, 2017, 20(3): 374-384.e375.

[22] SUGITA S, MANDAI M, HIRAMI Y, et al. HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration[J]. J Clin Med, 2020, 9(7).

[23] LI X J, LI C Y, BAI D, et al. Insights into stem cell therapy for diabetic retinopathy: a bibliometric and visual analysis[J]. Neural Regen Res, 2021, 16(1): 172-178.

[24] PAOLILLO S, MARSICO F, PRASTARO M, et al. Diabetic Cardiomyopathy: Definition, Diagnosis, and Therapeutic Implications[J]. Heart Fail Clin, 2019, 15(3): 341-347.

[25] JAKOB M, HAMBRECHT M, SPIEGEL J L, et al. Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Show Comparable Functionality to Their Autologous Origin[J]. Cells, 2020, 10(1).

[26] GUO S, ZHANG Y, ZHANG Y, et al. Multiple Intravenous Injections of Valproic Acid-Induced Mesenchymal Stem Cell from Human-Induced Pluripotent Stem Cells Improved Cardiac Function in an Acute Myocardial Infarction Rat Model[J]. Biomed Res Int, 2020, 2020: 2863501.

[27] TANG L, WANG H, DAI B, et al. Human induced pluripotent stem cell-derived cardiomyocytes reveal abnormal TGFβ signaling in type 2 diabetes mellitus[J]. J Mol Cell Cardiol, 2020, 142: 53-64.

[28] RONALDSON-BOUCHARD K, MA S P, YEAGER K, et al. Advanced maturation of human cardiac tissue grown from pluripotent stem cells[J]. Nature, 2018, 556(7700): 239-243.

[29] TSUKAMOTO Y, AKAGI T, AKASHI M. Vascularized cardiac tissue construction with orientation by layer-by-layer method and 3D printer[J]. Sci Rep, 2020, 10(1): 5484.

[30] YEUNG E, FUKUNISHI T, BAI Y, et al. Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo[J]. J Tissue Eng Regen Med, 2019, 13(11): 2031-2039.

[31] KUPFER M E, LIN W H, RAVIKUMAR V, et al. In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid[J]. Circ Res, 2020, 127(2): 207-224.

[32] TANG S W, TONG W Y, PANG S W, et al. Deconstructing, Replicating, and Engineering Tissue Microenvironment for Stem Cell Differentiation[J]. Tissue Eng Part B Rev, 2020.

[33] SCHWEIZER P A, DARCHE F F, ULLRICH N D, et al. Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells[J]. Stem Cell Res Ther, 2017, 8(1): 229.

[34] PROTZE S I, LIU J, NUSSINOVITCH U, et al. Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker[J]. Nat Biotechnol, 2017, 35(1): 56-68.

[35] CHAUVEAU S, ANYUKHOVSKY E P, BEN-ARI M, et al. Induced Pluripotent Stem Cell-Derived Cardiomyocytes Provide In Vivo Biological Pacemaker Function[J]. Circ Arrhythm Electrophysiol, 2017, 10(5): e004508.

[36] SCHULZE M L, LEMOINE M D, FISCHER A W, et al. Dissecting hiPSC-CM pacemaker function in a cardiac organoid model[J]. Biomaterials, 2019, 206: 133-145.

[37] DRAWNEL F M, BOCCARDO S, PRUMMER M, et al. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells[J]. Cell Rep, 2014, 9(3): 810-821.

[38] CHAMBERS S M, QI Y, MICA Y, et al. Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors[J]. Nat Biotechnol, 2012, 30(7): 715-720.

[39] LIU Q, SPUSTA S C, MI R, et al. Human neural crest stem cells derived from human ESCs and induced pluripotent stem cells: induction, maintenance, and differentiation into functional schwann cells[J]. Stem Cells Transl Med, 2012, 1(4): 266-278.

[40] KASHPUR O, SMITH A, GERAMI-NAINI B, et al. Differentiation of diabetic foot ulcer-derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes[J]. Faseb j, 2019, 33(1): 1262-1277.

[41] SHEN Y I, CHO H, PAPA A E, et al. Engineered human vascularized constructs accelerate diabetic wound healing[J]. Biomaterials, 2016, 102: 107-119.

[42] GORECKA J, GAO X, FEREYDOONI A, et al. Induced pluripotent stem cell-derived smooth muscle cells increase angiogenesis and accelerate diabetic wound healing[J]. Regen Med, 2020, 15(2): 1277-1293.

[43] XIA Y, NIVET E, SANCHO-MARTINEZ I, et al. Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells[J]. Nat Cell Biol, 2013, 15(12): 1507-1515.

[44] SONG B, SMINK A M, JONES C V, et al. The directed differentiation of human iPS cells into kidney podocytes[J]. PLoS One, 2012, 7(9): e46453.

[45] LAM A Q, FREEDMAN B S, MORIZANE R, et al. Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers[J]. J Am Soc Nephrol, 2014, 25(6): 1211-1225.

[46] SONG B, NICLIS J C, ALIKHAN M A, et al. Generation of induced pluripotent stem cells from human kidney mesangial cells[J]. J Am Soc Nephrol, 2011, 22(7): 1213-1220.

[47] TAJIRI S, YAMANAKA S, FUJIMOTO T, et al. Regenerative potential of induced pluripotent stem cells derived from patients undergoing haemodialysis in kidney regeneration[J]. Sci Rep, 2018, 8(1): 14919.

[48] LIU D, ZHENG W, PAN S, et al. Concise review: current trends on applications of stem cells in diabetic nephropathy[J]. Cell Death Dis, 2020, 11(11): 1000.

[49] TAKASATO M, ER P X, CHIU H S, et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis[J]. Nature, 2016, 536(7615): 238.

[50] CIAMPI O, IACONE R, LONGARETTI L, et al. Generation of functional podocytes from human induced pluripotent stem cells[J]. Stem Cell Res, 2016, 17(1): 130-139.

引用本文

王婉乔, 李彦欣, 诱导多能干细胞在糖尿病慢性并发症防治中基础研究进展[J]. 细胞与分子生物学研究, 2021; 1: (1) : 33-41.