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Urine-derived stem cell therapy for diabetes mellitus and its complications: progress and challenges

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Abstract

Diabetes mellitus (DM) is a chronic and relentlessly progressive metabolic disease characterized by a relative or absolute deficiency of insulin in the body, leading to increased production of advanced glycosylation end products that further enhance oxidative and nitrosative stresses, often leading to multiple macrovascular (cardiovascular disease) and microvascular (e.g., diabetic nephropathy, diabetic retinopathy, and neuropathy) complications, representing the ninth leading cause of death worldwide. Existing medical treatments do not provide a complete cure for DM; thus, stem cell transplantation therapy has become the focus of research on DM and its complications. Urine-derived stem cells (USCs), which are isolated from fresh urine and have biological properties similar to those of mesenchymal stem cells (MSCs), were demonstrated to exert antiapoptotic, antifibrotic, anti-inflammatory, and proangiogenic effects through direct differentiation or paracrine mechanisms and potentially treat patients with DM. USCs also have the advantages of simple noninvasive sample collection procedures, minimal ethical issues, low cost, and easy cell isolation methods and thus have received more attention in regenerative therapies in recent years. This review outlines the biological properties of USCs and the research progress and current limitations of their role in DM and related complications. In summary, USCs have shown good versatility in treating hyperglycemia-impaired target organs in preclinical models, and many challenges remain in translating USC therapies to the clinic.

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Abbreviations

DM:

Diabetes mellitus

USCs:

Urine-derived stem cells

MSCs:

Mesenchymal stem cells

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

SC:

Stem cell

IPCs:

Insulin-producing cells

iPSCs:

Induced pluripotent stem cells

ECM:

Extracellular matrix

EVs:

Extracellular vesicles

hUSCs:

Human USCs

USC-Exos:

USC-derived exosomes

BMSCs:

Bone mesenchymal stem cells

DCM:

Diabetic cardiomyopathy

DED:

Diabetic erectile dysfunction

DOP:

Diabetic osteoporosis

ESRD:

End-stage renal disease

miRNAs:

MicroRNAs

d-USC:

USCs from patients with DN

CCs:

Corpora cavernosa

LV:

Left ventricular

DR:

Diabetic retinopathy

References

  1. H. Sun, P. Saeedi, S. Karuranga, M. Pinkepank, K. Ogurtsova, B.B. Duncan, C. Stein, A. Basit, J.C.N. Chan, J.C. Mbanya, M.E. Pavkov, A. Ramachandaran, S.H. Wild, S. James, W.H. Herman, P. Zhang, C. Bommer, S. Kuo, E.J. Boyko, D.J. Magliano, IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract. 183, 109–119 (2022). https://doi.org/10.1016/j.diabres.2021.109119

    Article  Google Scholar 

  2. A.M. Shapiro, J.R. Lakey, E.A. Ryan, G.S. Korbutt, E. Toth, G.L. Warnock, N.M. Kneteman, R.V. Rajotte, Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343(4), 230–238 (2000). https://doi.org/10.1056/nejm200007273430401

    Article  CAS  PubMed  Google Scholar 

  3. M.R. Rickels, S.M. Kong, C. Fuller, C. Dalton-Bakes, J.F. Ferguson, M.P. Reilly, K.L. Teff, A. Naji, Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes. J. Clin. Endocrinol. Metab. 98(11), E1780–1785 (2013). https://doi.org/10.1210/jc.2013-1764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. M.R. Rickels, C. Fuller, C. Dalton-Bakes, E. Markmann, M. Palanjian, K. Cullison, J. Tiao, S. Kapoor, C. Liu, A. Naji, K.L. Teff, Restoration of glucose counterregulation by islet transplantation in long-standing type 1 diabetes. Diabetes 64(5), 1713–1718 (2015). https://doi.org/10.2337/db14-1620

    Article  CAS  PubMed  Google Scholar 

  5. B.J. Hering, W.R. Clarke, N.D. Bridges, T.L. Eggerman, R. Alejandro, M.D. Bellin, K. Chaloner, C.W. Czarniecki, J.S. Goldstein, L.G. Hunsicker, D.B. Kaufman, O. Korsgren, C.P. Larsen, X. Luo, J.F. Markmann, A. Naji, J. Oberholzer, A.M. Posselt, M.R. Rickels, C. Ricordi, M.A. Robien, P.A. Senior, A.M. Shapiro, P.G. Stock, N.A. Turgeon, Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care 39(7), 1230–1240 (2016). https://doi.org/10.2337/dc15-1988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. J.F. Markmann, M.R. Rickels, T.L. Eggerman, N.D. Bridges, D.E. Lafontant, J. Qidwai, E. Foster, W.R. Clarke, M. Kamoun, R. Alejandro, M.D. Bellin, K. Chaloner, C.W. Czarniecki, J.S. Goldstein, B.J. Hering, L.G. Hunsicker, D.B. Kaufman, O. Korsgren, C.P. Larsen, X. Luo, A. Naji, J. Oberholzer, A.M. Posselt, C. Ricordi, P.A. Senior, A.M.J. Shapiro, P.G. Stock, N.A. Turgeon, Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes. Am. J. Transplant. 21(4), 1477–1492 (2021). https://doi.org/10.1111/ajt.16174

    Article  CAS  PubMed  Google Scholar 

  7. Y.F. Smets, R.G. Westendorp, J.W. van der Pijl, F.T. de Charro, J. Ringers, J.W. de Fijter, H.H. Lemkes, Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure. Lancet 353(9168), 1915–1919 (1999). https://doi.org/10.1016/s0140-6736(98)07513-8

    Article  CAS  PubMed  Google Scholar 

  8. B.N. Becker, P.C. Brazy, Y.T. Becker, J.S. Odorico, T.J. Pintar, B.H. Collins, J.D. Pirsch, G.E. Leverson, D.M. Heisey, H.W. Sollinger, Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease. Kidney Int. 57(5), 2129–2135 (2000). https://doi.org/10.1046/j.1523-1755.2000.00064.x

    Article  CAS  PubMed  Google Scholar 

  9. R. Giannarelli, A. Coppelli, M.S. Sartini, M. Del Chiaro, F. Vistoli, G. Rizzo, M. Barsotti, S. Del Prato, F. Mosca, U. Boggi, P. Marchetti, Pancreas transplant alone has beneficial effects on retinopathy in type 1 diabetic patients. Diabetologia 49(12), 2977–2982 (2006). https://doi.org/10.1007/s00125-006-0463-5

    Article  CAS  PubMed  Google Scholar 

  10. R.P. Pelletier, A.A. Rajab, A. Diez, N.R. DiPaola, G.L. Bumgardner, E.A. Elkhammas, M.L. Henry, Early immunosuppression treatment correlates with later de novo donor-specific antibody development after kidney and pancreas transplantation. Clin. Transplant. 29(12), 1119–1127 (2015). https://doi.org/10.1111/ctr.12636

    Article  CAS  PubMed  Google Scholar 

  11. F. Vendrame, Y.Y. Hopfner, S. Diamantopoulos, S.K. Virdi, G. Allende, I.V. Snowhite, H.K. Reijonen, L. Chen, P. Ruiz, G. Ciancio, J.C. Hutton, S. Messinger, G.W. Burke 3rd, A. Pugliese, Risk factors for type 1 diabetes recurrence in immunosuppressed recipients of simultaneous pancreas-kidney transplants. Am. J. Transplant. 16(1), 235–245 (2016). https://doi.org/10.1111/ajt.13426

    Article  CAS  PubMed  Google Scholar 

  12. Y. Zhang, E. McNeill, H. Tian, S. Soker, K.E. Andersson, J.J. Yoo, A. Atala, Urine derived cells are a potential source for urological tissue reconstruction. J. Urol. 180(5), 2226–2233 (2008). https://doi.org/10.1016/j.juro.2008.07.023

    Article  CAS  PubMed  Google Scholar 

  13. S. Bharadwaj, G. Liu, Y. Shi, R. Wu, B. Yang, T. He, Y. Fan, X. Lu, X. Zhou, H. Liu, A. Atala, J. Rohozinski, Y. Zhang, Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology. Stem Cells 31(9), 1840–1856 (2013). https://doi.org/10.1002/stem.1424

    Article  CAS  PubMed  Google Scholar 

  14. H.S. Kang, S.H. Choi, B.S. Kim, J.Y. Choi, G.B. Park, T.G. Kwon, S.Y. Chun, Advanced properties of urine derived stem cells compared to adipose tissue derived stem cells in terms of cell proliferation, immune modulation and multi differentiation. J. Korean Med. Sci. 30(12), 1764–1776 (2015). https://doi.org/10.3346/jkms.2015.30.12.1764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. D. Zhang, G. Wei, P. Li, X. Zhou, Y. Zhang, Urine-derived stem cells: a novel and versatile progenitor source for cell-based therapy and regenerative medicine. Genes Dis. 1(1), 8–17 (2014). https://doi.org/10.1016/j.gendis.2014.07.001

    Article  PubMed  PubMed Central  Google Scholar 

  16. C. Wu, L. Chen, Y.Z. Huang, Y. Huang, O. Parolini, Q. Zhong, X. Tian, L. Deng, Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells. Stem Cells Int 2018, 7131532 (2018). https://doi.org/10.1155/2018/7131532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. A.J. Chen, J.K. Pi, J.G. Hu, Y.Z. Huang, H.W. Gao, S.F. Li, J. Li-Ling, H.Q. Xie, Identification and characterization of two morphologically distinct stem cell subpopulations from human urine samples. Sci. China Life Sci. 63(5), 712–723 (2020). https://doi.org/10.1007/s11427-018-9543-1

    Article  CAS  PubMed  Google Scholar 

  18. J. Zhou, X. Wang, S. Zhang, Y. Gu, L. Yu, J. Wu, T. Gao, F. Chen, Generation and characterization of human cryptorchid-specific induced pluripotent stem cells from urine. Stem Cells Dev. 22(5), 717–725 (2013). https://doi.org/10.1089/scd.2012.0260

    Article  CAS  PubMed  Google Scholar 

  19. M. Culenova, A. Nicodemou, Z.V. Novakova, M. Debreova, V. Smolinská, S. Bernatova, D. Ivanisova, O. Novotna, J. Vasicek, I. Varga, S. Ziaran, L. Danisovic, Isolation, culture and comprehensive characterization of biological properties of human urine-derived stem cells. Int. J. Mol. Sci. 22(22), 12503 (2021). https://doi.org/10.3390/ijms222212503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. J.J. Guan, X. Niu, F.X. Gong, B. Hu, S.C. Guo, Y.L. Lou, C.Q. Zhang, Z.F. Deng, Y. Wang, Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology. Tissue Eng. A 20(13-14), 1794–1806 (2014). https://doi.org/10.1089/ten.TEA.2013.0584

    Article  CAS  Google Scholar 

  21. G. Liu, R.A. Pareta, R. Wu, Y. Shi, X. Zhou, H. Liu, C. Deng, X. Sun, A. Atala, E.C. Opara, Y. Zhang, Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors. Biomaterials 34(4), 1311–1326 (2013). https://doi.org/10.1016/j.biomaterials.2012.10.038

    Article  CAS  PubMed  Google Scholar 

  22. B. Ouyang, X. Sun, D. Han, S. Chen, B. Yao, Y. Gao, J. Bian, Y. Huang, Y. Zhang, Z. Wan, B. Yang, H. Xiao, Z. Songyang, G. Liu, Y. Zhang, C. Deng, Human urine-derived stem cells alone or genetically-modified with FGF2 Improve type 2 diabetic erectile dysfunction in a rat model. PLoS One 9(3), e92825 (2014). https://doi.org/10.1371/journal.pone.0092825

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  23. E. Lazzeri, E. Ronconi, M.L. Angelotti, A. Peired, B. Mazzinghi, F. Becherucci, S. Conti, G. Sansavini, A. Sisti, F. Ravaglia, D. Lombardi, A. Provenzano, A. Manonelles, J.M. Cruzado, S. Giglio, R.M. Roperto, M. Materassi, L. Lasagni, P. Romagnani, Human urine-derived renal progenitors for personalized modeling of genetic kidney disorders. J. Am. Soc. Nephrol. 26(8), 1961–1974 (2015). https://doi.org/10.1681/asn.2014010057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. J.Y. Choi, S.Y. Chun, Y.S. Ha, D.H. Kim, J. Kim, P.H. Song, H.T. Kim, E.S. Yoo, B.S. Kim, T.G. Kwon, Potency of human urine-derived stem cells for renal lineage differentiation. Tissue Eng. Regen. Med. 14(6), 775–785 (2017). https://doi.org/10.1007/s13770-017-0081-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Y. Hwang, S.H. Cha, Y. Hong, A.R. Jung, H.S. Jun, Direct differentiation of insulin-producing cells from human urine-derived stem cells. Int. J. Med. Sci. 16(12), 1668–1676 (2019). https://doi.org/10.7150/ijms.36011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. G. Sun, B. Ding, M. Wan, L. Chen, J. Jackson, A. Atala, Formation and optimization of three-dimensional organoids generated from urine-derived stem cells for renal function in vitro. Stem Cell Res. Ther. 11(1), 309 (2020). https://doi.org/10.1186/s13287-020-01822-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. M. Zhou, L. Shen, Y. Qiao, Z. Sun, Inducing differentiation of human urine-derived stem cells into hepatocyte-like cells by coculturing with human hepatocyte L02 cells. J. Cell. Biochem. 121(1), 566–573 (2020). https://doi.org/10.1002/jcb.29301

    Article  CAS  PubMed  Google Scholar 

  28. D. Jafari, S. Malih, S.S. Eslami, R. Jafari, L. Darzi, P. Tarighi, A. Samadikuchaksaraei, The relationship between molecular content of mesenchymal stem cells derived exosomes and their potentials: Opening the way for exosomes based therapeutics. Biochimie 165, 76–89 (2019). https://doi.org/10.1016/j.biochi.2019.07.009

    Article  CAS  PubMed  Google Scholar 

  29. X. Dong, T. Zhang, Q. Liu, J. Zhu, J. Zhao, J. Li, B. Sun, G. Ding, X. Hu, Z. Yang, Y. Zhang, L. Li, Beneficial effects of urine-derived stem cells on fibrosis and apoptosis of myocardial, glomerular and bladder cells. Mol. Cell. Endocrinol. 427, 21–32 (2016). https://doi.org/10.1016/j.mce.2016.03.001

    Article  CAS  PubMed  Google Scholar 

  30. C.Y. Chen, S.S. Rao, L. Ren, X.K. Hu, Y.J. Tan, Y. Hu, J. Luo, Y.W. Liu, H. Yin, J. Huang, J. Cao, Z.X. Wang, Z.Z. Liu, H.M. Liu, S.Y. Tang, R. Xu, H. Xie, Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics 8(6), 1607–1623 (2018). https://doi.org/10.7150/thno.22958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. X. Li, J. Liao, X. Su, W. Li, Z. Bi, J. Wang, Q. Su, H. Huang, Y. Wei, Y. Gao, J. Li, L. Liu, C. Wang, Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1. Theranostics 10(21), 9561–9578 (2020). https://doi.org/10.7150/thno.42153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. K.C. Herold, D.A. Vignali, A. Cooke, J.A. Bluestone, Type 1 diabetes: translating mechanistic observations into effective clinical outcomes. Nat. Rev. Immunol. 13(4), 243–256 (2013). https://doi.org/10.1038/nri3422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. C.J. Nolan, P. Damm, M. Prentki, Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 378(9786), 169–181 (2011). https://doi.org/10.1016/s0140-6736(11)60614-4

    Article  PubMed  Google Scholar 

  34. Y. Yang, L. Chan, Monogenic diabetes: what it teaches us on the common forms of type 1 and type 2 diabetes. Endocr. Rev. 37(3), 190–222 (2016). https://doi.org/10.1210/er.2015-1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. K.A. D’Amour, A.G. Bang, S. Eliazer, O.G. Kelly, A.D. Agulnick, N.G. Smart, M.A. Moorman, E. Kroon, M.K. Carpenter, E.E. Baetge, Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat. Biotechnol. 24(11), 1392–1401 (2006). https://doi.org/10.1038/nbt1259

    Article  CAS  PubMed  Google Scholar 

  36. D. Zhang, W. Jiang, M. Liu, X. Sui, X. Yin, S. Chen, Y. Shi, H. Deng, Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res. 19(4), 429–438 (2009). https://doi.org/10.1038/cr.2009.28

    Article  CAS  PubMed  Google Scholar 

  37. S. Hrvatin, C.W. O’Donnell, F. Deng, J.R. Millman, F.W. Pagliuca, P. DiIorio, A. Rezania, D.K. Gifford, D.A. Melton, Differentiated human stem cells resemble fetal, not adult, β cells. Proc. Natl Acad. Sci. USA 111(8), 3038–3043 (2014). https://doi.org/10.1073/pnas.1400709111

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  38. A. Rezania, J.E. Bruin, P. Arora, A. Rubin, I. Batushansky, A. Asadi, S. O’Dwyer, N. Quiskamp, M. Mojibian, T. Albrecht, Y.H. Yang, J.D. Johnson, T.J. Kieffer, Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat. Biotechnol. 32(11), 1121–1133 (2014). https://doi.org/10.1038/nbt.3033

    Article  CAS  PubMed  Google Scholar 

  39. L. Sui, N. Danzl, S.R. Campbell, R. Viola, D. Williams, Y. Xing, Y. Wang, N. Phillips, G. Poffenberger, B. Johannesson, J. Oberholzer, A.C. Powers, R.L. Leibel, X. Chen, M. Sykes, D. Egli, β-cell replacement in mice using human type 1 diabetes nuclear transfer embryonic stem cells. Diabetes 67(1), 26–35 (2018). https://doi.org/10.2337/db17-0120

    Article  CAS  PubMed  Google Scholar 

  40. Y.M. Park, C.M. Yang, H.Y. Cho, Therapeutic effects of insulin-producing human umbilical cord-derived mesenchymal stem cells in a type 1 diabetes mouse model. Int. J. Mol. Sci. 23(13), 6877 (2022). https://doi.org/10.3390/ijms23136877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. D. Balboa, T. Barsby, V. Lithovius, J. Saarimäki-Vire, M. Omar-Hmeadi, O. Dyachok, H. Montaser, P.E. Lund, M. Yang, H. Ibrahim, A. Näätänen, V. Chandra, H. Vihinen, E. Jokitalo, J. Kvist, J. Ustinov, A.I. Nieminen, E. Kuuluvainen, V. Hietakangas, P. Katajisto, J. Lau, P.O. Carlsson, S. Barg, A. Tengholm, T. Otonkoski, Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. Nat. Biotechnol. 40(7), 1042–1055 (2022). https://doi.org/10.1038/s41587-022-01219-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. T. Shi, M. Cheung, Urine-derived induced pluripotent/neural stem cells for modeling neurological diseases. Cell Biosci. 11(1), 85 (2021). https://doi.org/10.1186/s13578-021-00594-5

    Article  PubMed  PubMed Central  Google Scholar 

  43. T. Zhao, D. Luo, Y. Sun, X. Niu, Y. Wang, C. Wang, W. Jia, Human urine-derived stem cells play a novel role in the treatment of STZ-induced diabetic mice. J. Mol. Histol. 49(4), 419–428 (2018). https://doi.org/10.1007/s10735-018-9772-5

    Article  CAS  PubMed  Google Scholar 

  44. R.A. Galhom, H.E. Korayem, M.A. Ibrahim, A. Abd-Eltawab Tammam, M.M. Khalifa, E.K. Rashwan, M.H. Al Badawi, Urine-derived stem cells versus their lysate in ameliorating erectile dysfunction in a rat model of type 2 diabetes. Front. Physiol. 13, 854949 (2022). https://doi.org/10.3389/fphys.2022.854949

    Article  PubMed  PubMed Central  Google Scholar 

  45. Z.Z. Jiang, Y.M. Liu, X. Niu, J.Y. Yin, B. Hu, S.C. Guo, Y. Fan, Y. Wang, N.S. Wang, Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats. Stem Cell Res. Ther. 7, 24 (2016). https://doi.org/10.1186/s13287-016-0287-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. R. Wu, M. Soland, G. Liu, Y. Shi, C. Zhang, Y. Tang, G. Almeida-Porada, Y. Zhang, Functional characterization of the immunomodulatory properties of human urine-derived stem cells. Transl. Androl. Urol. 10(9), 3566–3578 (2021). https://doi.org/10.21037/tau-21-506

    Article  PubMed  PubMed Central  Google Scholar 

  47. C. Zhou, X.R. Wu, H.S. Liu, X.H. Liu, G.H. Liu, X.B. Zheng, T. Hu, Z.X. Liang, X.W. He, X.J. Wu, L.C. Smith, Y. Zhang, P. Lan, Immunomodulatory effect of urine-derived stem cells on inflammatory bowel diseases via downregulating Th1/Th17 Immune Responses in a PGE2-dependent Manner. J. Crohns. Colitis 14(5), 654–668 (2020). https://doi.org/10.1093/ecco-jcc/jjz200

    Article  PubMed  Google Scholar 

  48. B. Ouyang, Y. Xie, C. Zhang, C. Deng, L. Lv, J. Yao, Y. Zhang, G. Liu, J. Deng, C. Deng, Extracellular vesicles from human urine-derived stem cells ameliorate erectile dysfunction in a diabetic rat model by delivering proangiogenic MicroRNA. Sex. Med. 7(2), 241–250 (2019). https://doi.org/10.1016/j.esxm.2019.02.001

    Article  PubMed  PubMed Central  Google Scholar 

  49. G. Xiong, L. Tao, W.J. Ma, M.J. Gong, L. Zhao, L.J. Shen, C.L. Long, D.Y. Zhang, Y.Y. Zhang, G.H. Wei, Urine-derived stem cells for the therapy of diabetic nephropathy mouse model. Eur. Rev. Med. Pharmacol. Sci. 24(3), 1316–1324 (2020). https://doi.org/10.26355/eurrev_202002_20189

    Article  CAS  PubMed  Google Scholar 

  50. Y.R. Duan, B.P. Chen, F. Chen, S.X. Yang, C.Y. Zhu, Y.L. Ma, Y. Li, J. Shi, Exosomal microRNA-16-5p from human urine-derived stem cells ameliorates diabetic nephropathy through protection of podocyte. J. Cell. Mol. Med. 25(23), 10798–10813 (2021). https://doi.org/10.1111/jcmm.14558

    Article  CAS  PubMed  Google Scholar 

  51. Y. Fu, J. Guan, S. Guo, F. Guo, X. Niu, Q. Liu, C. Zhang, H. Nie, Y. Wang, Human urine-derived stem cells in combination with polycaprolactone/gelatin nanofibrous membranes enhance wound healing by promoting angiogenesis. J. Transl. Med. 12, 274 (2014). https://doi.org/10.1186/s12967-014-0274-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Y. Zhang, X. Niu, X. Dong, Y. Wang, H. Li, Bioglass enhanced wound healing ability of urine-derived stem cells through promoting paracrine effects between stem cells and recipient cells. J. Tissue Eng. Regen. Med. 12(3), e1609–e1622 (2018). https://doi.org/10.1002/term.2587

    Article  CAS  PubMed  Google Scholar 

  53. X.R. Zhang, Y.Z. Huang, H.W. Gao, Y.L. Jiang, J.G. Hu, J.K. Pi, A.J. Chen, Y. Zhang, L. Zhou, H.Q. Xie, Hypoxic preconditioning of human urine-derived stem cell-laden small intestinal submucosa enhances wound healing potential. Stem Cell Res. Ther. 11(1), 150 (2020). https://doi.org/10.1186/s13287-020-01662-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. C. Zhang, D. Luo, T. Li, Q. Yang, Y. Xie, H. Chen, L. Lv, J. Yao, C. Deng, X. Liang, R. Wu, X. Sun, Y. Zhang, C. Deng, G. Liu, Transplantation of human urine-derived stem cells ameliorates erectile function and cavernosal endothelial function by promoting autophagy of corpus cavernosal endothelial cells in diabetic erectile dysfunction rats. Stem Cells Int 2019, 2168709 (2019). https://doi.org/10.1155/2019/2168709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. D. Zhang, J. Du, M. Yu, L. Suo, Urine-derived stem cells-extracellular vesicles ameliorate diabetic osteoporosis through HDAC4/HIF-1α/VEGFA axis by delivering microRNA-26a-5p. Cell Biol. Toxicol. (2022). https://doi.org/10.1007/s10565-022-09713-5

  56. R.A. DeFronzo, W.B. Reeves, A.S. Awad, Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors. Nat. Rev. Nephrol. 17(5), 319–334 (2021). https://doi.org/10.1038/s41581-021-00393-8

    Article  CAS  PubMed  Google Scholar 

  57. Y.S. Kanwar, L. Sun, P. Xie, F.Y. Liu, S. Chen, A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu. Rev. Pathol. 6, 395–423 (2011). https://doi.org/10.1146/annurev.pathol.4.110807.092150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. F.P. Schena, L. Gesualdo, Pathogenetic mechanisms of diabetic nephropathy. J. Am. Soc. Nephrol. 16(Suppl 1), S30–33 (2005). https://doi.org/10.1681/asn.2004110970

    Article  CAS  PubMed  Google Scholar 

  59. S. Wang, Y. Li, J. Zhao, J. Zhang, Y. Huang, Mesenchymal stem cells ameliorate podocyte injury and proteinuria in a type 1 diabetic nephropathy rat model. Biol. Blood Marrow Transplant. 19(4), 538–546 (2013). https://doi.org/10.1016/j.bbmt.2013.01.001

    Article  CAS  PubMed  Google Scholar 

  60. L. Peng, Y. Chen, S. Shi, H. Wen, Stem cell-derived and circulating exosomal microRNAs as new potential tools for diabetic nephropathy management. Stem Cell Res. Ther. 13(1), 25 (2022). https://doi.org/10.1186/s13287-021-02696-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. S. Wang, X. Wen, X.R. Han, Y.J. Wang, M. Shen, S.H. Fan, J. Zhuang, Z.F. Zhang, Q. Shan, M.Q. Li, B. Hu, C.H. Sun, D.M. Wu, J. Lu, Y.L. Zheng, Repression of microRNA-382 inhibits glomerular mesangial cell proliferation and extracellular matrix accumulation via FoxO1 in mice with diabetic nephropathy. Cell Prolif. 51(5), e12462 (2018). https://doi.org/10.1111/cpr.12462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Q. Zhu, Q. Li, X. Niu, G. Zhang, X. Ling, J. Zhang, Y. Wang, Z. Deng, Extracellular vesicles secreted by human urine-derived stem cells promote ischemia repair in a mouse model of hind-limb ischemia. Cell. Physiol. Biochem. 47(3), 1181–1192 (2018). https://doi.org/10.1159/000490214

    Article  CAS  PubMed  Google Scholar 

  63. G. Xiong, W. Tang, D. Zhang, D. He, G. Wei, A. Atala, X.J. Liang, A.J. Bleyer, M.E. Bleyer, J. Yu, J.A. Aloi, J.X. Ma, C.M. Furdui, Y. Zhang, Impaired regeneration potential in urinary stem cells diagnosed from the patients with diabetic nephropathy. Theranostics 9(14), 4221–4232 (2019). https://doi.org/10.7150/thno.34050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. G. Broughton 2nd, J.E. Janis, C.E. Attinger, Wound healing: an overview. Plast. Reconstr. Surg. 117(7 Suppl), 1e–S-32e-S (2006). https://doi.org/10.1097/01.prs.0000222562.60260.f9

    Article  CAS  PubMed  Google Scholar 

  65. T.A. Mustoe, K. O’Shaughnessy, O. Kloeters, Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast. Reconstr. Surg. 117(7 Suppl), 35s–41s (2006). https://doi.org/10.1097/01.prs.0000225431.63010.1b

    Article  CAS  PubMed  Google Scholar 

  66. J. Holl, C. Kowalewski, Z. Zimek, P. Fiedor, A. Kaminski, T. Oldak, M. Moniuszko, A. Eljaszewicz, Chronic diabetic wounds and their treatment with skin substitutes. Cells 10(3), 655 (2021). https://doi.org/10.3390/cells10030655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. D. Baltzis, I. Eleftheriadou, A. Veves, Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv. Ther. 31(8), 817–836 (2014). https://doi.org/10.1007/s12325-014-0140-x

    Article  CAS  PubMed  Google Scholar 

  68. Y.M. Cao, M.Y. Liu, Z.W. Xue, Y. Qiu, J. Li, Y. Wang, Q.K. Wu, Surface-structured bacterial cellulose loaded with hUSCs accelerate skin wound healing by promoting angiogenesis in rats. Biochem. Biophys. Res. Commun. 516(4), 1167–1174 (2019). https://doi.org/10.1016/j.bbrc.2019.06.161

    Article  CAS  PubMed  Google Scholar 

  69. J.M. Souren, M. Ponec, R: van Wijk, Contraction of collagen by human fibroblasts and keratinocytes. Vitr. Cell. Dev. Biol. 25(11), 1039–1045 (1989). https://doi.org/10.1007/bf02624138

    Article  CAS  Google Scholar 

  70. H. Brem, M. Tomic-Canic, Cellular and molecular basis of wound healing in diabetes. J. Clin. Invest. 117(5), 1219–1222 (2007). https://doi.org/10.1172/jci32169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. R.R. Driskell, B.M. Lichtenberger, E. Hoste, K. Kretzschmar, B.D. Simons, M. Charalambous, S.R. Ferron, Y. Herault, G. Pavlovic, A.C. Ferguson-Smith, F.M. Watt, Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature 504(7479), 277–281 (2013). https://doi.org/10.1038/nature12783

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  72. B. Bucalo, W.H. Eaglstein, V. Falanga, Inhibition of cell proliferation by chronic wound fluid. Wound Repair. Regen. 1(3), 181–186 (1993). https://doi.org/10.1046/j.1524-475X.1993.10308.x

    Article  CAS  PubMed  Google Scholar 

  73. N.J. Trengove, H. Bielefeldt-Ohmann, M.C. Stacey, Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair. Regen. 8(1), 13–25 (2000). https://doi.org/10.1046/j.1524-475x.2000.00013.x

    Article  CAS  PubMed  Google Scholar 

  74. G.S. Schultz, A. Wysocki, Interactions between extracellular matrix and growth factors in wound healing. Wound Repair. Regen. 17(2), 153–162 (2009). https://doi.org/10.1111/j.1524-475X.2009.00466.x

    Article  PubMed  Google Scholar 

  75. Y. Kouidrat, D. Pizzol, T. Cosco, T. Thompson, M. Carnaghi, A. Bertoldo, M. Solmi, B. Stubbs, N. Veronese, High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies. Diabet. Med 34(9), 1185–1192 (2017). https://doi.org/10.1111/dme.13403

    Article  CAS  PubMed  Google Scholar 

  76. V.S. Thorve, A.D. Kshirsagar, N.S. Vyawahare, V.S. Joshi, K.G. Ingale, R.J. Mohite, Diabetes-induced erectile dysfunction: epidemiology, pathophysiology and management. J. Diabetes Complic. 25(2), 129–136 (2011). https://doi.org/10.1016/j.jdiacomp.2010.03.003

    Article  Google Scholar 

  77. J.J. Joseph, S.H. Golden, Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Ann. N. Y. Acad. Sci. 1391(1), 20–34 (2017). https://doi.org/10.1111/nyas.13217

    Article  PubMed  ADS  Google Scholar 

  78. J. Zhuang, P. Gao, H. Chen, Z. Fang, J. Zheng, D. Zhu, J. Hou, Extracellular vesicles from human urine-derived stem cells merged in hyaluronic acid ameliorate erectile dysfunction in type 2 diabetic rats by glans administration. Andrology 10(8), 1673–1686 (2022). https://doi.org/10.1111/andr.13293

    Article  CAS  PubMed  Google Scholar 

  79. Q. Yang, W. Chen, D. Han, C. Zhang, Y. Xie, X. Sun, G. Liu, C. Deng, Intratunical injection of human urine-derived stem cells derived exosomes prevents fibrosis and improves erectile function in a rat model of Peyronie’s disease. Andrologia 52(11), e13831 (2020). https://doi.org/10.1111/and.13831

    Article  CAS  PubMed  Google Scholar 

  80. S.C. DeShields, T.D. Cunningham, Comparison of osteoporosis in US adults with type 1 and type 2 diabetes mellitus. J. Endocrinol. Invest. 41(9), 1051–1060 (2018). https://doi.org/10.1007/s40618-018-0828-x

    Article  CAS  PubMed  Google Scholar 

  81. R. Ma, R. Zhu, L. Wang, Y. Guo, C. Liu, H. Liu, F. Liu, H. Li, Y. Li, M. Fu, D. Zhang, Diabetic osteoporosis: a review of its traditional Chinese medicinal use and clinical and preclinical research. Evid.-Based Complement. Altern. Med. 2016, 3218313 (2016). https://doi.org/10.1155/2016/3218313

    Article  Google Scholar 

  82. V.V. Shanbhogue, S. Hansen, M. Frost, K. Brixen, A.P. Hermann, Bone disease in diabetes: another manifestation of microvascular disease? Lancet Diabetes Endocrinol. 5(10), 827–838 (2017). https://doi.org/10.1016/s2213-8587(17)30134-1

    Article  PubMed  Google Scholar 

  83. J.H. Kim, A.R. Kim, Y.H. Choi, S. Jang, G.H. Woo, J.H. Cha, E.J. Bak, Y.J. Yoo, Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. PLoS One 12(12), e0189702 (2017). https://doi.org/10.1371/journal.pone.0189702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. S.E. Kahn, B. Zinman, J.M. Lachin, S.M. Haffner, W.H. Herman, R.R. Holman, B.G. Kravitz, D. Yu, M.A. Heise, R.P. Aftring, G. Viberti, Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care 31(5), 845–851 (2008). https://doi.org/10.2337/dc07-2270

    Article  CAS  PubMed  Google Scholar 

  85. C.Y. Chen, S.S. Rao, Y.J. Tan, M.J. Luo, X.K. Hu, H. Yin, J. Huang, Y. Hu, Z.W. Luo, Z.Z. Liu, Z.X. Wang, J. Cao, Y.W. Liu, H.M. Li, Y. Chen, W. Du, J.H. Liu, Y. Zhang, T.H. Chen, H.M. Liu, B. Wu, T. Yue, Y.Y. Wang, K. Xia, P.F. Lei, S.Y. Tang, H. Xie, Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG. Bone Res. 7, 18 (2019). https://doi.org/10.1038/s41413-019-0056-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. S. Rubler, J. Dlugash, Y.Z. Yuceoglu, T. Kumral, A.W. Branwood, A. Grishman, New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am. J. Cardiol. 30(6), 595–602 (1972). https://doi.org/10.1016/0002-9149(72)90595-4

    Article  CAS  PubMed  Google Scholar 

  87. W.B. Kannel, M. Hjortland, W.P. Castelli, Role of diabetes in congestive heart failure: the Framingham study. Am. J. Cardiol. 34(1), 29–34 (1974). https://doi.org/10.1016/0002-9149(74)90089-7

    Article  CAS  PubMed  Google Scholar 

  88. Y. Tan, Z. Zhang, C. Zheng, K.A. Wintergerst, B.B. Keller, L. Cai, Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nat. Rev. Cardiol. 17(9), 585–607 (2020). https://doi.org/10.1038/s41569-020-0339-2

    Article  PubMed  PubMed Central  Google Scholar 

  89. E. Konduracka, G. Cieslik, D. Galicka-Latala, P. Rostoff, A. Pietrucha, P. Latacz, G. Gajos, M.T. Malecki, J. Nessler, Myocardial dysfunction and chronic heart failure in patients with long-lasting type 1 diabetes: a 7-year prospective cohort study. Acta Diabetol. 50(4), 597–606 (2013). https://doi.org/10.1007/s00592-013-0455-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. S. Bouthoorn, G.B. Valstar, A. Gohar, H.M. den Ruijter, H.B. Reitsma, A.W. Hoes, F.H. Rutten, The prevalence of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction in men and women with type 2 diabetes: a systematic review and meta-analysis. Diabetes Vasc. Dis. Res. 15(6), 477–493 (2018). https://doi.org/10.1177/1479164118787415

    Article  Google Scholar 

  91. W.H. Dillmann, Diabetic cardiomyopathy. Circ. Res. 124(8), 1160–1162 (2019). https://doi.org/10.1161/circresaha.118.314665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. D.C. Raev, Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy? An echocardiographic study of young type I diabetic patients. Diabetes Care 17(7), 633–639 (1994). https://doi.org/10.2337/diacare.17.7.633

    Article  CAS  PubMed  Google Scholar 

  93. M. E. Hölscher, C. Bode, H. Bugger, Diabetic cardiomyopathy: does the type of diabetes matter? Int. J. Mol. Sci. 17(12) (2016). https://doi.org/10.3390/ijms17122136

  94. G. Jia, M.A. Hill, J.R. Sowers, Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ. Res. 122(4), 624–638 (2018). https://doi.org/10.1161/circresaha.117.311586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. L.V. Heerebeek, N. Hamdani, M.L. Handoko, I. Falcao-Pires, W.J.J.C. Paulus, Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation 117(1), 43–51 (2008). https://doi.org/10.1161/circulationaha.107.728550

    Article  PubMed  Google Scholar 

  96. B. Vulesevic, B. McNeill, F. Giacco, K. Maeda, N.J. Blackburn, M. Brownlee, R.W. Milne, E.J. Suuronen, Methylglyoxal-induced endothelial cell loss and inflammation contribute to the development of diabetic cardiomyopathy. Diabetes 65(6), 1699–1713 (2016). https://doi.org/10.2337/db15-0568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. A. Wan, B. Rodrigues, Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy. Cardiovasc. Res. 111(3), 172–183 (2016). https://doi.org/10.1093/cvr/cvw159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. J.W. Yau, S.L. Rogers, R. Kawasaki, E.L. Lamoureux, J.W. Kowalski, T. Bek, S.J. Chen, J.M. Dekker, A. Fletcher, J. Grauslund, S. Haffner, R.F. Hamman, M.K. Ikram, T. Kayama, B.E. Klein, R. Klein, S. Krishnaiah, K. Mayurasakorn, J.P. O’Hare, T.J. Orchard, M. Porta, M. Rema, M.S. Roy, T. Sharma, J. Shaw, H. Taylor, J.M. Tielsch, R. Varma, J.J. Wang, N. Wang, S. West, L. Xu, M. Yasuda, X. Zhang, P. Mitchell, T.Y. Wong, Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35(3), 556–564 (2012). https://doi.org/10.2337/dc11-1909

    Article  PubMed  PubMed Central  Google Scholar 

  99. A.W. Stitt, T.M. Curtis, M. Chen, R.J. Medina, G.J. McKay, A. Jenkins, T.A. Gardiner, T.J. Lyons, H.P. Hammes, R. Simó, N. Lois, The progress in understanding and treatment of diabetic retinopathy. Prog. Retin. Eye Res. 51, 156–186 (2016). https://doi.org/10.1016/j.preteyeres.2015.08.001

    Article  PubMed  Google Scholar 

  100. J. Lechner, O.E. O’Leary, A.W. Stitt, The pathology associated with diabetic retinopathy. Vis. Res 139, 7–14 (2017). https://doi.org/10.1016/j.visres.2017.04.003

    Article  PubMed  Google Scholar 

  101. T. Hamadneh, S. Aftab, N. Sherali, R. Vetrivel Suresh, N. Tsouklidis, M. An, Choroidal changes in diabetic patients with different stages of diabetic retinopathy. Cureus 12(10), e10871 (2020). https://doi.org/10.7759/cureus.10871

    Article  PubMed  PubMed Central  Google Scholar 

  102. D.A. Antonetti, P.S. Silva, A.W. Stitt, Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat. Rev. Endocrinol. 17(4), 195–206 (2021). https://doi.org/10.1038/s41574-020-00451-4

    Article  PubMed  PubMed Central  Google Scholar 

  103. X. Gu, X. Yu, C. Zhao, P. Duan, T. Zhao, Y. Liu, S. Li, Z. Yang, Y. Li, C. Qian, Z. Yin, Y. Wang, Efficacy and safety of autologous bone marrow mesenchymal stem cell transplantation in patients with diabetic retinopathy. Cell. Physiol. Biochem. 49(1), 40–52 (2018). https://doi.org/10.1159/000492838

    Article  CAS  PubMed  Google Scholar 

  104. B. Mathew, S. Ravindran, X. Liu, L. Torres, M. Chennakesavalu, C.C. Huang, L. Feng, R. Zelka, J. Lopez, M. Sharma, S. Roth, Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion. Biomaterials 197, 146–160 (2019). https://doi.org/10.1016/j.biomaterials.2019.01.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. C.H. Gil, D. Chakraborty, C.P. Vieira, N. Prasain, S. Li Calzi, S.D. Fortmann, P. Hu, K. Banno, M. Jamal, C. Huang, M.S. Sielski, Y. Lin, X. Huang, M.D. Dupont, J.L. Floyd, R. Prasad, A.L.F. Longhini, T.J. McGill, H.M. Chung, M.P. Murphy, D.N. Kotton, M.E. Boulton, M.C. Yoder, M.B. Grant, Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice. Sci. Adv. 8(9), eabm5559 (2022). https://doi.org/10.1126/sciadv.abm5559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. S. Bharadwaj, G. Liu, Y. Shi, C. Markert, K.E. Andersson, A. Atala, Y. Zhang, Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue Eng. A 17(15-16), 2123–2132 (2011). https://doi.org/10.1089/ten.TEA.2010.0637

    Article  Google Scholar 

  107. S.F. Tian, Z.Z. Jiang, Y.M. Liu, X. Niu, B. Hu, S.C. Guo, N.S. Wang, Y. Wang, Human urine-derived stem cells contribute to the repair of ischemic acute kidney injury in rats. Mol. Med. Rep. 16(4), 5541–5548 (2017). https://doi.org/10.3892/mmr.2017.7240

    Article  CAS  PubMed  Google Scholar 

  108. M. Talmon, E. Massara, G. Pruonto, M. Quaregna, F. Boccafoschi, B. Riva, L.G. Fresu, Characterization of a functional Ca(2+) toolkit in urine-derived stem cells and derived skeletal muscle cells. Cell Calcium 103, 102548 (2022). https://doi.org/10.1016/j.ceca.2022.102548

    Article  CAS  PubMed  Google Scholar 

  109. G. Liu, X. Wang, X. Sun, C. Deng, A. Atala, Y. Zhang, The effect of urine-derived stem cells expressing VEGF loaded in collagen hydrogels on myogenesis and innervation following after subcutaneous implantation in nude mice. Biomaterials 34(34), 8617–8629 (2013). https://doi.org/10.1016/j.biomaterials.2013.07.077

    Article  CAS  PubMed  Google Scholar 

  110. X. Ling, G. Zhang, Y. Xia, Q. Zhu, J. Zhang, Q. Li, X. Niu, G. Hu, Y. Yang, Y. Wang, Z. Deng, Exosomes from human urine-derived stem cells enhanced neurogenesis via miR-26a/HDAC6 axis after ischaemic stroke. J. Cell. Mol. Med. 24(1), 640–654 (2020). https://doi.org/10.1111/jcmm.14774

    Article  CAS  PubMed  Google Scholar 

  111. W. Chen, M. Xie, B. Yang, S. Bharadwaj, L. Song, G. Liu, S. Yi, G. Ye, A. Atala, Y. Zhang, Skeletal myogenic differentiation of human urine-derived cells as a potential source for skeletal muscle regeneration. J. Tissue Eng. Regen. Med. 11(2), 334–341 (2017). https://doi.org/10.1002/term.1914

    Article  CAS  PubMed  Google Scholar 

  112. R. Wu, C. Huang, Q. Wu, X. Jia, M. Liu, Z. Xue, Y. Qiu, X. Niu, Y. Wang, Exosomes secreted by urine-derived stem cells improve stress urinary incontinence by promoting repair of pubococcygeus muscle injury in rats. Stem Cell Res. Ther. 10(1), 80 (2019). https://doi.org/10.1186/s13287-019-1182-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. G. Liu, R. Wu, B. Yang, Y. Shi, C. Deng, A. Atala, S. Mou, T. Criswell, Y. Zhang, A cocktail of growth factors released from a heparin hyaluronic-acid hydrogel promotes the myogenic potential of human urine-derived stem cells in vivo. Acta Biomater. 107, 50–64 (2020). https://doi.org/10.1016/j.actbio.2020.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by The Key Research and development project of Jiangxi Province [grant number 20201BBG71006] and the National Natural Science Foundation of China (Grant number 81460018).

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  1. Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, China

    Yun Zou, Shanshan Li, Wen Chen & Jixiong Xu

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J.X. contributed to the study of conception and design. Material preparation, data collection and analysis were performed by Y.Z. and S.L. W.C. prepared the table and figure. The first draft of the manuscript was written by all authors and all authors commented on previous versions of the manuscript. J.X. contributed to Writing-review, editing and supervision. All authors read and approved the final manuscript.

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Zou, Y., Li, S., Chen, W. et al. Urine-derived stem cell therapy for diabetes mellitus and its complications: progress and challenges. Endocrine 83, 270–284 (2024). https://doi.org/10.1007/s12020-023-03552-y

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