Secretome Derived from Mesenchymal Stem/Stromal Cells: A Promising Strategy for Diabetes and its Complications


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Abstract

:Diabetes is a complex metabolic disease with a high global prevalence. The health and quality of life of patients with diabetes are threatened by many complications, including diabetic foot ulcers, diabetic kidney diseases, diabetic retinopathy, and diabetic peripheral neuropathy. The application of mesenchymal stem/stromal cells (MSCs) in cell therapies has been recognized as a potential treatment for diabetes and its complications. MSCs were originally thought to exert biological effects exclusively by differentiating and replacing specific impaired cells. However, the paracrine function of factors secreted by MSCs may exert additional protective effects. MSCs secrete multiple compounds, including proteins, such as growth factors, chemokines, and other cytokines; nucleic acids, such as miRNAs; and lipids, extracellular vesicles (EVs), and exosomes (Exos). Collectively, these secreted compounds are called the MSC secretome, and usage of these chemicals in cell-free therapies may provide stronger effects with greater safety and convenience. Recent studies have demonstrated positive effects of the MSC secretome, including improved insulin sensitivity, reduced inflammation, decreased endoplasmic reticulum stress, enhanced M2 polarization of macrophages, and increased angiogenesis and autophagy; however, the mechanisms leading to these effects are not fully understood. This review summarizes the current research regarding the secretome derived from MSCs, including efforts to quantify effectiveness and uncover potential molecular mechanisms in the treatment of diabetes and related disorders. In addition, limitations and challenges are also discussed so as to facilitate applications of the MSC secretome as a cell-free therapy for diabetes and its complications.

About the authors

ling li

Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital

Email: info@benthamscience.net

Siyu Hua

Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital

Email: info@benthamscience.net

Lianghui You

Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital

Author for correspondence.
Email: info@benthamscience.net

Tianying Zhong

Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital

Author for correspondence.
Email: info@benthamscience.net

References

  1. Sun, H.; Saeedi, P.; Karuranga, S. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract., 2022, 183, 109119. doi: 10.1016/j.diabres.2021.109119 PMID: 34879977
  2. Todd, J.A. Etiology of type 1 diabetes. Immunity, 2010, 32(4), 457-467. doi: 10.1016/j.immuni.2010.04.001 PMID: 20412756
  3. Van Belle, T.L.; Coppieters, K.T.; Von Herrath, M.G. Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiol. Rev., 2011, 91(1), 79-118. doi: 10.1152/physrev.00003.2010 PMID: 21248163
  4. J D C. Diagnosis and classification of diabetes mellitusJ. 2014, 81-90.
  5. Kolb, H.; Mandrup-Poulsen, T. An immune origin of type 2 diabetes? Diabetologia, 2005, 48(6), 1038-1050. doi: 10.1007/s00125-005-1764-9 PMID: 15864529
  6. Melendez-Ramirez, L.Y.; Richards, R.J.; Cefalu, W.T. Complications of type 1 diabetes. Endocrinol. Metab. Clin. North Am., 2010, 39(3), 625-640. doi: 10.1016/j.ecl.2010.05.009 PMID: 20723824
  7. He, S.; Wang, J.; Zhang, X. Long-term influence of type 2 diabetes and metabolic syndrome on all-cause and cardiovascular death, and microvascular and macrovascular complications in Chinese adults — A 30-year follow-up of the Da Qing diabetes study. Diabetes Res. Clin. Pract., 2022, 191, 110048. doi: 10.1016/j.diabres.2022.110048 PMID: 36029887
  8. Donath, M.Y.; Dinarello, C.A.; Mandrup-Poulsen, T. Targeting innate immune mediators in type 1 and type 2 diabetes. Nat. Rev. Immunol., 2019, 19(12), 734-746. doi: 10.1038/s41577-019-0213-9 PMID: 31501536
  9. Huang, H.; Shang, Y.; Li, H. Co-transplantation of islets-laden microgels and biodegradable O 2 -generating microspheres for diabetes treatment. ACS Appl. Mater. Interfaces, 2022, 14(34), 38448-38458. doi: 10.1021/acsami.2c07215 PMID: 35980755
  10. Horwitz, E.M.; Le Blanc, K.; Dominici, M. Clarification of the nomenclature for MSC: The international society for cellular therapy position statement. Cytotherapy, 2005, 7(5), 393-395. doi: 10.1080/14653240500319234 PMID: 16236628
  11. Zhao, K.; Lin, R.; Fan, Z. Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: A multicenter, randomized, phase 3, open-label trial. J. Hematol. Oncol., 2022, 15(1), 22. doi: 10.1186/s13045-022-01240-4 PMID: 35255929
  12. Kim, H.J.; Cho, K.R.; Jang, H. Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: A phase I clinical trial. Alzheimers Res. Ther., 2021, 13(1), 154. doi: 10.1186/s13195-021-00897-2 PMID: 34521461
  13. Barnhoorn, M.C.; Wasser, M.N.J.M.; Roelofs, H. Long-term evaluation of allogeneic bone marrow-derived mesenchymal stromal cell therapy for crohn’s disease perianal fistulas. J. Crohn’s Colitis, 2020, 14(1), 64-70. doi: 10.1093/ecco-jcc/jjz116 PMID: 31197361
  14. Kassem, D.H.; Habib, S.A.; Badr, O.I. Isolation of rat adipose tissue mesenchymal stem cells for differentiation into insulin-producing cells. J. J Vis. Exp., 2022, 186.
  15. Poursafavi, Z.; Abroun, S.; Kaviani, S.; Hayati Roodbari, N. Differentiation of alginate-encapsulated wharton jelly-derived mesenchymal stem cells into insulin producing cells. Cell J., 2022, 24(8), 449-457. J PMID: 36093804
  16. Rodprasert, W.; Nantavisai, S.; Pathanachai, K.; Pavasant, P.; Osathanon, T.; Sawangmake, C. Tailored generation of insulin producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue. Sci. Rep., 2021, 11(1), 12409. doi: 10.1038/s41598-021-91774-3 PMID: 34117315
  17. Liang, R.Y.; Zhang, K.L.; Chuang, M.H. A one-step, monolayer culture and chemical-based approach to generate insulin-producing cells from human adipose-derived stem cells to mitigate hyperglycemia in STZ-induced diabetic rats. Cell Transplant., 2022, 31. doi: 10.1177/09636897221106995 PMID: 36002988
  18. Kim, S.Y.; Kim, Y.R.; Park, W.J. Characterisation of insulin-producing cells differentiated from tonsil derived mesenchymal stem cells. Differentiation, 2015, 90(1-3), 27-39. doi: 10.1016/j.diff.2015.08.001 PMID: 26391447
  19. Karagyaur, M.; Dzhauari, S.; Basalova, N. MSC secretome as a promising tool for neuroprotection and neuroregeneration in a model of intracerebral hemorrhage. Pharmaceutics, 2021, 13(12), 2031. doi: 10.3390/pharmaceutics13122031 PMID: 34959314
  20. Park, H.; Chugh, R.M.; El Andaloussi, A. Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model. Sci. Rep., 2021, 11(1), 4525. doi: 10.1038/s41598-021-84216-7 PMID: 33633319
  21. Eiro, N.; Fraile, M.; González-Jubete, A.; González, L.O.; Vizoso, F.J. Mesenchymal (Stem) stromal cells based as new therapeutic alternative in inflammatory bowel disease: Basic mechanisms, experimental and clinical evidence, and challenges. Int. J. Mol. Sci., 2022, 23(16), 8905. doi: 10.3390/ijms23168905 PMID: 36012170
  22. Viswanathan, S.; Shi, Y.; Galipeau, J. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy, 2019, 21(10), 1019-1024. doi: 10.1016/j.jcyt.2019.08.002 PMID: 31526643
  23. Kawada-Horitani, E.; Kita, S.; Okita, T. Human adipose-derived mesenchymal stem cells prevent type 1 diabetes induced by immune checkpoint blockade. Diabetologia, 2022, 65(7), 1185-1197. doi: 10.1007/s00125-022-05708-3 PMID: 35511238
  24. Liu, Y.; Chen, J.; Liang, H. Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling. Stem Cell Res. Ther., 2022, 13(1), 258. doi: 10.1186/s13287-022-02927-8 PMID: 35715841
  25. Sun, Y.L.; Shang, L.R.; Liu, R.H. Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes. World J. Stem Cells, 2022, 14(1), 104-116. doi: 10.4252/wjsc.v14.i1.104 PMID: 35126831
  26. Elshemy, M.; Asem, M.; Allemailem, K. Antioxidative capacity of liver- and adipose-derived mesenchymal stem cell-conditioned media and their applicability in treatment of type 2. Diabetic RatsJ, 2021, 2021, 8833467.
  27. Yin, Y.; Hao, H.; Cheng, Y. Human umbilical cord-derived mesenchymal stem cells direct macrophage polarization to alleviate pancreatic islets dysfunction in type 2 diabetic mice. Cell Death Dis., 2018, 9(7), 760. doi: 10.1038/s41419-018-0801-9 PMID: 29988034
  28. Chahal, J.; Gómez-Aristizábal, A.; Shestopaloff, K. Bone marrow mesenchymal stromal cell treatment in patients with osteoarthritis results in overall improvement in pain and symptoms and reduces synovial inflammation. Stem Cells Transl. Med., 2019, 8(8), 746-757. doi: 10.1002/sctm.18-0183 PMID: 30964245
  29. Baak, L.M.; Wagenaar, N.; van der Aa, N.E. Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): A first-in-human, open-label intervention study. Lancet Neurol., 2022, 21(6), 528-536. doi: 10.1016/S1474-4422(22)00117-X PMID: 35568047
  30. Izadi, M.; Sadr Hashemi Nejad, A.; Moazenchi, M. Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: A phase I/II randomized placebo-controlled clinical trial. Stem Cell Res. Ther., 2022, 13(1), 264. doi: 10.1186/s13287-022-02941-w PMID: 35725652
  31. Deng, D.; Zhang, P.; Guo, Y.; Lim, T.O. A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis. Ann. Rheum. Dis., 2017, 76(8), 1436-1439. doi: 10.1136/annrheumdis-2017-211073 PMID: 28478399
  32. Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
  33. Carlsson, P.O.; Schwarcz, E.; Korsgren, O.; Le Blanc, K. Preserved β-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes, 2015, 64(2), 587-592. doi: 10.2337/db14-0656 PMID: 25204974
  34. Zang, L.; Li, Y.; Hao, H. Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: A single-center, double-blinded, randomized, placebo-controlled phase II trial. Stem Cell Res. Ther., 2022, 13(1), 180. doi: 10.1186/s13287-022-02848-6 PMID: 35505375
  35. Zhang, C.; Huang, L.; Wang, X. Topical and intravenous administration of human umbilical cord mesenchymal stem cells in patients with diabetic foot ulcer and peripheral arterial disease: A phase I pilot study with a 3-year follow-up. Stem Cell Res. Ther., 2022, 13(1), 451. doi: 10.1186/s13287-022-03143-0 PMID: 36064461
  36. Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
  37. Chan, A.M.L.; Sampasivam, Y.; Lokanathan, Y. Biodistribution of mesenchymal stem cells (MSCs) in animal models and implied role of exosomes following systemic delivery of MSCs: A systematic review. Am. J. Transl. Res., 2022, 14(4), 2147-2161. J PMID: 35559383
  38. Ammar, H.I.; Shamseldeen, A.M.; Shoukry, H.S. Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats. Am. J. Physiol. Heart Circ. Physiol., 2021, 320(4), H1290-H1302. doi: 10.1152/ajpheart.00317.2020 PMID: 33513084
  39. Du, S.; Zeugolis, D.I.; O’Brien, T. Scaffold-based delivery of mesenchymal stromal cells to diabetic wounds. Stem Cell Res. Ther., 2022, 13(1), 426. doi: 10.1186/s13287-022-03115-4 PMID: 35987712
  40. Nazarie Ignat, S.R.; Gharbia, S.; Hermenean, A.; Dinescu, S.; Costache, M. Regenerative potential of mesenchymal stem cells’ (MSCs) Secretome for liver fibrosis therapies. Int. J. Mol. Sci., 2021, 22(24), 13292. doi: 10.3390/ijms222413292 PMID: 34948088
  41. Liao, H.J.; Chang, C.H.; Huang, C.Y.F.; Chen, H.T. Potential of using infrapatellar–fat–pad–derived mesenchymal stem cells for therapy in degenerative arthritis: Chondrogenesis, exosomes, and transcription regulation. Biomolecules, 2022, 12(3), 386. doi: 10.3390/biom12030386 PMID: 35327578
  42. Delavogia, E.; Ntentakis, D.P.; Cortinas, J.A.; Fernandez-Gonzalez, A.; Alex Mitsialis, S.; Kourembanas, S. Mesenchymal stromal/stem cell extracellular vesicles and perinatal injury: One formula for many diseases. Stem Cells, 2022, 40(11), 991-1007. doi: 10.1093/stmcls/sxac062 PMID: 36044737
  43. Asgari Taei, A.; Khodabakhsh, P.; Nasoohi, S.; Farahmandfar, M.; Dargahi, L. Paracrine effects of mesenchymal stem cells in ischemic stroke: Opportunities and challenges. Mol. Neurobiol., 2022, 59(10), 6281-6306. doi: 10.1007/s12035-022-02967-4 PMID: 35922728
  44. An, T.; Chen, Y.; Tu, Y.; Lin, P. Mesenchymal stromal cell-derived extracellular vesicles in the treatment of diabetic foot ulcers: Application and challenges. Stem Cell Rev. Rep., 2021, 17(2), 369-378. doi: 10.1007/s12015-020-10014-9 PMID: 32772239
  45. Deng, H.; Sun, C.; Sun, Y. Lipid, protein, and microRNA composition within mesenchymal stem cell-derived exosomes. Cell. Reprogram., 2018, 20(3), 178-186. doi: 10.1089/cell.2017.0047 PMID: 29782191
  46. Bogatcheva, N.V.; Coleman, M.E. Conditioned medium of mesenchymal stromal cells: A new class of therapeutics. Biochemistry, 2019, 84(11), 1375-1389. doi: 10.1134/S0006297919110129 PMID: 31760924
  47. Lui, P.P.Y.; Leung, Y.T. Practical considerations for translating mesenchymal stromal cell-derived extracellular vesicles from bench to bed. Pharmaceutics, 2022, 14(8), 1684. doi: 10.3390/pharmaceutics14081684 PMID: 36015310
  48. Brunello, G.; Zanotti, F.; Trentini, M. Exosomes derived from dental pulp stem cells show different angiogenic and osteogenic properties in relation to the age of the donor. Pharmaceutics, 2022, 14(5), 908. doi: 10.3390/pharmaceutics14050908 PMID: 35631496
  49. Wang, Y.; Zhang, L.; Wu, Y. Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants. Stem Cell Res. Ther., 2020, 11(1), 414. doi: 10.1186/s13287-020-01931-0 PMID: 32967723
  50. Seo, Y.; Shin, T.; Ahn, J. Human tonsil-derived mesenchymal stromal cells maintain proliferating and ros-regulatory properties via stanniocalcin-1. J.Cells, 2020, 9(3), 636.
  51. Bi, Y.; Qiao, X.; Liu, Q. Systemic proteomics and miRNA profile analysis of exosomes derived from human pluripotent stem cells. Stem Cell Res. Ther., 2022, 13(1), 449. doi: 10.1186/s13287-022-03142-1 PMID: 36064647
  52. Pires, A.O.; Mendes-Pinheiro, B.; Teixeira, F.G. Unveiling the differences of secretome of human bone marrow mesenchymal stem cells, adipose tissue-derived stem cells, and human umbilical cord perivascular cells: A proteomic analysis. Stem Cells Dev., 2016, 25(14), 1073-1083. doi: 10.1089/scd.2016.0048 PMID: 27226274
  53. Konala, V.B.R.; Bhonde, R.; Pal, R. Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. In Vitro Cell. Dev. Biol. Anim., 2020, 56(9), 689-700. doi: 10.1007/s11626-020-00501-1 PMID: 33006709
  54. Wang, S.; Umrath, F.; Cen, W.; Salgado, A.J.; Reinert, S.; Alexander, D. Pre-conditioning with IFN-γ and hypoxia enhances the angiogenic potential of iPSC-Derived MSC Secretome. Cells, 2022, 11(6), 988. doi: 10.3390/cells11060988 PMID: 35326438
  55. Widjaja, S.L.; Salimo, H.; Yulianto, I. Soetrisno. Proteomic analysis of hypoxia and non-hypoxia secretome mesenchymal stem-like cells from human breastmilk. Saudi J. Biol. Sci., 2021, 28(8), 4399-4407. doi: 10.1016/j.sjbs.2021.04.034 PMID: 34354424
  56. Zhang, B.; Tian, X.; Qu, Z.; Hao, J.; Zhang, W. Hypoxia-preconditioned extracellular vesicles from mesenchymal stem cells improve cartilage repair in osteoarthritis. Membranes, 2022, 12(2), 225. doi: 10.3390/membranes12020225 PMID: 35207146
  57. Even, K.M.; Gaesser, A.M.; Ciamillo, S.A.; Linardi, R.L.; Ortved, K.F. Comparing the immunomodulatory properties of equine BM-MSCs culture expanded in autologous platelet lysate, pooled platelet lysate, equine serum and fetal bovine serum supplemented culture media. Front. Vet. Sci., 2022, 9, 958724. doi: 10.3389/fvets.2022.958724 PMID: 36090170
  58. Asgari Taei, A.; Dargahi, L.; Khodabakhsh, P.; Kadivar, M.; Farahmandfar, M. Hippocampal neuroprotection mediated by secretome of human mesenchymal stem cells against experimental stroke. CNS Neurosci. Ther., 2022, 28(9), 1425-1438. doi: 10.1111/cns.13886 PMID: 35715988
  59. Papait, A.; Ragni, E.; Cargnoni, A. Comparison of EV-free fraction, EVs, and total secretome of amniotic mesenchymal stromal cells for their immunomodulatory potential: A translational perspective. Front. Immunol., 2022, 13, 960909. doi: 10.3389/fimmu.2022.960909 PMID: 36052081
  60. Lin, H.; Chen, H.; Zhao, X. Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration. J. Transl. Med., 2021, 19(1), 456. doi: 10.1186/s12967-021-03125-5 PMID: 34736500
  61. Sun, X.; Li, K.; Aryal, U.K.; Li, B.Y.; Yokota, H. PI3K-activated MSC proteomes inhibit mammary tumors via Hsp90ab1 and Myh9. Mol. Ther. Oncolytics, 2022, 26, 360-371. doi: 10.1016/j.omto.2022.08.003 PMID: 36090473
  62. Tan, H.L.; Guan, X.H.; Hu, M. Human amniotic mesenchymal stem cells-conditioned medium protects mice from high-fat diet-induced obesity. Stem Cell Res. Ther., 2021, 12(1), 364. doi: 10.1186/s13287-021-02437-z PMID: 34174964
  63. Obendorf, J.; Fabian, C.; Thome, U.H.; Laube, M. Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells. Stem Cell Res. Ther., 2020, 11(1), 525. doi: 10.1186/s13287-020-02028-4 PMID: 33298180
  64. Huang, J; U KP; Yang, F Human pluripotent stem cell-derived ectomesenchymal stromal cells promote more robust functional recovery than umbilical cord-derived mesenchymal stromal cells after hypoxic-ischaemic brain damage. Theranostics, 2022, 12(1), 143-166. doi: 10.7150/thno.57234 PMID: 34987639
  65. De Gregorio, C.; Contador, D.; Díaz, D. Human adipose-derived mesenchymal stem cell-conditioned medium ameliorates polyneuropathy and foot ulceration in diabetic BKS db/db mice. Stem Cell Res. Ther., 2020, 11(1), 168.
  66. Chen, H.; Zhang, H.; Zheng, Y. Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-κB-dependent mechanism. Cell Death Dis., 2020, 11(3), 188. doi: 10.1038/s41419-020-2378-3 PMID: 32179740
  67. Ti, D.; Hao, H.; Tong, C. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J. Transl. Med., 2015, 13, 308.
  68. Elshaer, S.; Evans, W.; Pentecost, M. Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2 mouseJ. Stem Cell Res. Ther., 2018, 9(1), 322.
  69. Liu, W.; Yu, M.; Xie, D. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res. Ther., 2020, 11(1), 259. doi: 10.1186/s13287-020-01756-x PMID: 32600435
  70. Shao, H.; Im, H.; Castro, C.M.; Breakefield, X.; Weissleder, R.; Lee, H. New technologies for analysis of extracellular vesicles. Chem. Rev., 2018, 118(4), 1917-1950. doi: 10.1021/acs.chemrev.7b00534 PMID: 29384376
  71. Hade, M.D.; Suire, C.N.; Mossell, J.; Suo, Z. Extracellular vesicles: Emerging frontiers in wound healing. Med. Res. Rev., 2022, 42(6), 2102-2125. doi: 10.1002/med.21918 PMID: 35757979
  72. Kahmini, F.R.; Shahgaldi, S. Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles as novel cell-free therapy for treatment of autoimmune disorders. Exp. Mol. Pathol., 2021, 118, 104566. doi: 10.1016/j.yexmp.2020.104566 PMID: 33160961
  73. Lin, Z.; Wu, Y.; Xu, Y.; Li, G.; Li, Z.; Liu, T. Mesenchymal stem cell-derived exosomes in cancer therapy resistance: Recent advances and therapeutic potential. Mol. Cancer, 2022, 21(1), 179. doi: 10.1186/s12943-022-01650-5 PMID: 36100944
  74. Karami fath, M; Anjomrooz, M; Taha, SR The therapeutic effect of exosomes from mesenchymal stem cells on colorectal cancer: Toward cell-free therapy. Pathol Res Pract, 2022, 237, 154024. doi: 10.1016/j.prp.2022.154024 PMID: 35905664
  75. Wei, H.; Chen, F.; Chen, J. Mesenchymal stem cell derived exosomes as nanodrug carrier of doxorubicin for targeted osteosarcoma therapy via SDF1-CXCR4 Axis. Int. J. Nanomedicine, 2022, 17, 3483-3495. doi: 10.2147/IJN.S372851 PMID: 35959282
  76. Su, Y.; Silva, J.D.; Doherty, D. Mesenchymal stromal cells-derived extracellular vesicles reprogramme macrophages in ARDS models through the miR-181a-5p-PTEN-pSTAT5-SOCS1 axis. Thorax, 2022, 78(6), 617-630. PMID: 35948417
  77. Ma, X.; Wang, Y.; Shi, Y. Exosomal miR-132-3p from mesenchymal stromal cells improves synaptic dysfunction and cognitive decline in vascular dementia. Stem Cell Res. Ther., 2022, 13(1), 315. doi: 10.1186/s13287-022-02995-w PMID: 35841005
  78. He, Q.; Wang, L.; Zhao, R. Retracted article: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy. Stem Cell Res. Ther., 2020, 11(1), 223. doi: 10.1186/s13287-020-01731-6 PMID: 32513303
  79. Ebrahim, N.; Ahmed, I.; Hussien, N. Mesenchymal stem cell-derived exosomes ameliorated diabetic nephropathy by autophagy induction through the mtor signaling pathway. Cells, 2018, 7(12), 226.
  80. Li, B.; Luan, S.; Chen, J. The MSC-Derived exosomal lncRNA H19 promotes wound healing in diabetic foot ulcers by upregulating PTEN via MicroRNA-152-3p. Mol. Ther. Nucleic Acids, 2020, 19, 814-826. doi: 10.1016/j.omtn.2019.11.034 PMID: 31958697
  81. Chen, Y.; Ding, H.; Wei, M. MSC-Secreted exosomal H19 promotes trophoblast cell invasion and migration by downregulating let-7b and upregulating FOXO1. Mol. Ther. Nucleic Acids, 2020, 19, 1237-1249. doi: 10.1016/j.omtn.2019.11.031 PMID: 32069774
  82. Zhang, Q.; Cao, L.; Zou, S. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles carrying MicroRNA-181c-5p Promote BMP2-Induced repair of cartilage injury through inhibition of SMAD7 expression. Stem Cells Int., 2022, 2022, 1-14. doi: 10.1155/2022/1157498 PMID: 35782228
  83. Yin, S.; Liu, W.; Ji, C. hucMSC-sEVs-Derived 14-3-3ζ serves as a bridge between yap and autophagy in diabetic kidney disease. Oxid. Med. Cell. Longev., 2022, 2022, 1-18. doi: 10.1155/2022/3281896 PMID: 36199425
  84. Garcia, S.G.; Sandoval-Hellín, N.; Clos-Sansalvador, M. Mesenchymal stromal cells induced regulatory B cells are enriched in extracellular matrix genes and IL-10 independent modulators. Front. Immunol., 2022, 13, 957797. doi: 10.3389/fimmu.2022.957797 PMID: 36189264
  85. Jiang, Y.; Hong, S.; Zhu, X. IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension. Front. Immunol., 2022, 13, 940093. doi: 10.3389/fimmu.2022.940093 PMID: 36203611
  86. Lu, T.; Zhang, J.; Cai, J. Extracellular vesicles derived from mesenchymal stromal cells as nanotherapeutics for liver ischaemia–reperfusion injury by transferring mitochondria to modulate the formation of neutrophil extracellular traps. Biomaterials, 2022, 284, 121486. doi: 10.1016/j.biomaterials.2022.121486 PMID: 35447404
  87. Nickel, S.; Christ, M.; Schmidt, S. Human mesenchymal stromal cells resolve lipid load in high fat diet-induced non-alcoholic steatohepatitis in mice by mitochondria donation. Cells, 2022, 11(11), 1829. doi: 10.3390/cells11111829 PMID: 35681524
  88. Hashemi, S.; Hassan, Z.; Hossein-Khannazer, N. Investigating the route of administration and efficacy of adipose tissue-derived mesenchymal stem cells and conditioned medium in type 1 diabetic mice. Inflammopharmacology, 2020, 28(2), 585-601.
  89. Cooper, T; Sherman, S; Bell, G Ultrafiltration and injection of islet regenerative stimuli secreted by pancreatic mesenchymal stromal cellsJ 2021, 30(5), 247-64.
  90. Gao, X.; Song, L.; Shen, K. Bone marrow mesenchymal stem cells promote the repair of islets from diabetic mice through paracrine actions. Mol. Cell. Endocrinol., 2014, 338(1-2), 41-50.
  91. Nojehdehi, S.; Soudi, S.; Hesampour, A.; Rasouli, S.; Soleimani, M.; Hashemi, S.M. Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes. J. Cell. Biochem., 2018, 119(11), 9433-9443. doi: 10.1002/jcb.27260 PMID: 30074271
  92. Keshtkar, S.; Kaviani, M.; Sarvestani, F.S. Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function. EXCLI J., 2020, 19, 1064-1080. J PMID: 33013264
  93. Alkaabi, J.; Sharma, C.; Yasin, J. Relationship between lipid profile, inflammatory and endothelial dysfunction biomarkers, and type 1 diabetes mellitus: A case-control study. Am. J. Transl. Res., 2022, 14(7), 4838-4847. J PMID: 35958469
  94. Hu, X.F.; Xiang, G.; Wang, T.J. Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: Critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice. Theranostics, 2021, 11(8), 3796-3812. doi: 10.7150/thno.50907 PMID: 33664862
  95. Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
  96. Gao, D.; Jiao, J.; Wang, Z. The roles of cell-cell and organ-organ crosstalk in the type 2 diabetes mellitus associated inflammatory microenvironment. Cytokine Growth Factor Rev., 2022, 66, 15-25. doi: 10.1016/j.cytogfr.2022.04.002 PMID: 35459618
  97. Bhatti, J.S.; Sehrawat, A.; Mishra, J. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic. Biol. Med., 2022, 184, 114-134. doi: 10.1016/j.freeradbiomed.2022.03.019 PMID: 35398495
  98. Polovina, M.M.; Potpara, T.S. Endothelial dysfunction in metabolic and vascular disorders. Postgrad. Med., 2014, 126(2), 38-53. doi: 10.3810/pgm.2014.03.2739 PMID: 24685967
  99. Yuan, Y.; Shi, M.; Li, L. Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1α pathway. Clin. Sci., 2016, 130(23), 2181-2198. doi: 10.1042/CS20160235 PMID: 27613156
  100. Sanap, A.; Bhonde, R.; Joshi, K. Conditioned medium of adipose derived mesenchymal stem cells reverse insulin resistance through downregulation of stress induced serine kinases. Eur. J. Pharmacol., 2020, 881, 173215. doi: 10.1016/j.ejphar.2020.173215 PMID: 32473166
  101. Kim, H.J.; Li, Q.; Song, W.J. Fibroblast growth factor-1 as a mediator of paracrine effects of canine adipose tissue-derived mesenchymal stem cells on in vitro-induced insulin resistance models. BMC Vet. Res., 2018, 14(1), 351. doi: 10.1186/s12917-018-1671-1 PMID: 30445954
  102. Shree, N.; Bhonde, R.R. Conditioned media from adipose tissue derived mesenchymal stem cells reverse insulin resistance in cellular models. J. Cell. Biochem., 2017, 118(8), 2037-2043. doi: 10.1002/jcb.25777 PMID: 27791278
  103. Kim, K.S.; Choi, Y.K.; Kim, M.J. Umbilical cord-mesenchymal stem cell-conditioned medium improves insulin resistance in C2C12 Cell. Diabetes Metab. J., 2021, 45(2), 260-269. doi: 10.4093/dmj.2019.0191 PMID: 32662257
  104. Sun, Y.; Shi, H.; Yin, S. Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving β-Cell destruction. ACS Nano, 2018, 12(8), 7613-7628. doi: 10.1021/acsnano.7b07643 PMID: 30052036
  105. Liu, Z.; Han, J.; Wang, Y.; Yang, M.; Niu, L.; Shi, B. Association of serum C1Q/TNF-related protein 4 levels with carotid atherosclerosis in subjects with type 2 diabetes mellitus: A cross-sectional study. Clin. Chim. Acta, 2022, 531, 337-341. doi: 10.1016/j.cca.2022.04.1004 PMID: 35525266
  106. Riveline, J.; Vergés, B.; Detournay, B. Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study. Diabetes Metab., 2022, 48(3), 101306. doi: 10.1016/j.diabet.2021.101306 PMID: 34813929
  107. Sela, Y.; Grinberg, K.; Cukierman-Yaffe, T.; Natovich, R. Relationship between cognitive function in individuals with diabetic foot ulcer and mortality. Diabetol. Metab. Syndr., 2022, 14(1), 133. doi: 10.1186/s13098-022-00901-1 PMID: 36123752
  108. Lytvyn, Y.; Albakr, R.; Bjornstad, P. Renal hemodynamic dysfunction and neuropathy in longstanding type 1 diabetes: Results from the Canadian study of longevity in type 1 diabetes. J. Diabetes Complications, 2022, 36(11), 108320. doi: 10.1016/j.jdiacomp.2022.108320 PMID: 36201892
  109. Li, X.Y.; Zhang, X.T.; Jiao, Y.C. In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder. World J. Diabetes, 2022, 13(8), 622-642. doi: 10.4239/wjd.v13.i8.622 PMID: 36159224
  110. Tuglo, L.S. Prevalence and determinants of lower extremity amputations among type I and type II diabetic patients: A multicenter-based study. Int. Wound J., 2022, 20(4), 903-909. PMID: 36054437
  111. Pastar, I.; Balukoff, N.C.; Marjanovic, J. Molecular pathophysiology of chronic wounds: Current state and future directions. Cold Spring Harb. Perspect. Biol., 2022, 15(4), a041243. PMID: 36123031
  112. Huang, J.; Zhang, S.; Ding, X. Research progress on the mechanism by which skin macrophage dysfunction mediates chronic inflammatory injury in diabetic skin. Front. Endocrinol., 2022, 13, 960551. doi: 10.3389/fendo.2022.960551 PMID: 36093074
  113. Gao, D.; Xie, J.; Zhang, J. MSC attenuate diabetes-induced functional impairment in adipocytes via secretion of insulin-like growth factor-1. Biochem. Biophys. Res. Commun., 2014, 452(1), 99-105. doi: 10.1016/j.bbrc.2014.08.060 PMID: 25152396
  114. You, H.; Namgoong, S.; Han, S. Wound-healing potential of human umbilical cord blood-derived mesenchymal stromal cells in vitro-a pilot study J. Cytotherapy, 2015, 17(11), 1506-1513. J
  115. Kinoshita, K.; Kuno, S.; Ishimine, H. Therapeutic potential of adipose-derived SSEA-3-Positive muse cells for treating diabetic skin ulcers. Stem Cells Transl. Med., 2015, 14(2), 146-155.
  116. Kato, Y.; Iwata, T.; Morikawa, S. Allogeneic transplantation of an adipose-derived stem cell sheet combined with artificial skin accelerates wound healing in a rat wound model of type 2 diabetes and obesity. Diabetes, 2015, 64(8), 2723-2734.
  117. De Mayo, T.; Conget, P.; Becerra-Bayona, S. The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice. PLoS One, 2017, 12(6), e0177533.
  118. Bailey, A.; Li, H.; Kirkham, A. MSC-Derived Extracellular Vesicles to heal diabetic wounds: A systematic review and meta-analysis of preclinical animal studies. Stem Cell Rev. Rep., 2022, 18(3), 968-979.
  119. Yu, M.; Liu, W.; Li, J. Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway. Stem Cell Res. Ther., 2020, 11(1), 350. doi: 10.1186/s13287-020-01824-2 PMID: 32787917
  120. Pomatto, M.; Gai, C.; Negro, F. Differential therapeutic effect of extracellular vesicles derived by bone marrow and adipose mesenchymal stem cells on wound healing of diabetic ulcers and correlation to their cargoes. Int. J. Mol. Sci., 2021, 22(8), 3851. doi: 10.3390/ijms22083851 PMID: 33917759
  121. Hu, J.; Liu, X.; Chi, J. Resveratrol enhances wound healing in type 1 diabetes mellitus by promoting the expression of extracellular vesicle-carried MicroRNA-129 derived from mesenchymal stem cells. J. Proteome Res., 2022, 21(2), 313-324.
  122. Karalliedde, J.; Winocour, P.; Chowdhury, T.A. Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease. Diabet. Med., 2022, 39(4), e14769. doi: 10.1111/dme.14769 PMID: 35080257
  123. Inker, L.A.; Astor, B.C.; Fox, C.H. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am. J. Kidney Dis., 2014, 63(5), 713-735. doi: 10.1053/j.ajkd.2014.01.416 PMID: 24647050
  124. Li, H.; Rong, P.; Ma, X. Mouse umbilical cord mesenchymal stem cell paracrine alleviates renal fibrosis in diabetic nephropathy by reducing myofibroblast transdifferentiation and cell proliferation and upregulating mmps in mesangial cellsJ. J. Diabetes Res., 2020, 2020, 3847171.
  125. Lv, S.; Liu, G.; Sun, A. Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7. Diab. Vasc. Dis. Res., 2014, 11(4), 251-261.
  126. Lv, S.; Cheng, J.; Sun, A. Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting oxidative stress. Diabetes Res. Clin. Pract., 2014, 104(1), 143-154.
  127. Xiang, E.; Han, B.; Zhang, Q. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res. Ther., 2020, 11(1), 336.
  128. Bai, Y.; Wang, J.; He, Z. Mesenchymal stem cells reverse diabetic nephropathy disease via lipoxin a4 by targeting transforming growth factor β (tgf-β)/smad pathway and pro-inflammatory cytokines. Med. Sci. Monit., 2019, 25, 3069-3076.
  129. Konari, N.; Nagaishi, K.; Kikuchi, S. Mitochondria transfer from mesenchymal stem cells structurally and functionally repairs renal proximal tubular epithelial cells in diabetic nephropathy in vivo. Sci. Rep., 2019, 9(1), 5184.
  130. Park, J.; Hwang, I.; Hwang, S. Human umbilical cord blood-derived mesenchymal stem cells prevent diabetic renal injury through paracrine action. Diabetes Res. Clin. Pract., 2012, 98(3), 465-473.
  131. Nagaishi, K.; Mizue, Y.; Chikenji, T. Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes. Sci. Rep., 2016, 6(1), 34842. doi: 10.1038/srep34842 PMID: 27721418
  132. Grange, C.; Tritta, S.; Tapparo, M. Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy. Sci. Rep., 2019, 9(1), 4468.
  133. Hao, Y.; Miao, J.; Liu, W. Mesenchymal stem cell-derived exosomes carry microRNA-125a to protect against diabetic nephropathy by targeting histone deacetylase 1 and downregulating endothelin-1. Diabetes Metab. Syndr. Obes., 2021, 14, 1405-1418.
  134. Zhong, L.; Liao, G.; Wang, X. Mesenchymal stem cells–microvesicle-miR-451a ameliorate early diabetic kidney injury by negative regulation of P15 and P19. Exp. Biol. Med., 2018, 243(15-16), 1233-1242. doi: 10.1177/1535370218819726 PMID: 30614256
  135. Zhang, Y.; Le, X.; Zheng, S. MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization. Stem Cell Res. Ther., 2022, 13(1), 171.
  136. Cai, X.; Zou, F.; Xuan, R. Exosomes from mesenchymal stem cells expressing microribonucleic acid-125b inhibit the progression of diabetic nephropathy via the tumour necrosis factor receptor-associated factor 6/Akt axis. Endocr. J., 2021, 68(7), 817-828.
  137. McGurnaghan, S.J.; Blackbourn, L.A.K.; Caparrotta, T.M. Cohort profile: The Scottish diabetes research network national diabetes cohort – a population-based cohort of people with diabetes in scotland. BMJ Open, 2022, 12(10), e063046. doi: 10.1136/bmjopen-2022-063046 PMID: 36223968
  138. Blonde, L.; Umpierrez, G.E.; Reddy, S.S. American association of clinical endocrinology clinical practice guideline: Developing a diabetes mellitus comprehensive care plan—2022 update. Endocr. Pract., 2022, 28(10), 923-1049. doi: 10.1016/j.eprac.2022.08.002 PMID: 35963508
  139. Omori, K.; Nagata, N.; Kurata, K. Inhibition of stromal cell–derived factor-1α/CXCR4 signaling restores the blood-retina barrier in pericyte-deficient mouse retinas. JCI Insight, 2018, 3(23), e120706. doi: 10.1172/jci.insight.120706 PMID: 30518679
  140. Yao, J.; Wu, X.; Yu, Q. The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo. Sci. Adv., 2022, 8(21), eabn6928. doi: 10.1126/sciadv.abn6928 PMID: 35622925
  141. Song, J.; Huang, B.B.; Ong, J.X.; Konopek, N.; Fawzi, A.A. Hemodynamic effects of anti-vascular endothelial growth factor injections on optical coherence tomography angiography in diabetic macular edema eyes. Transl. Vis. Sci. Technol., 2022, 11(10), 5. doi: 10.1167/tvst.11.10.5 PMID: 36180027
  142. Cheng, Y.; Du, Y.; Liu, H.; Tang, J.; Veenstra, A.; Kern, T.S. Photobiomodulation inhibits long-term structural and functional lesions of diabetic retinopathy. Diabetes, 2018, 67(2), 291-298. doi: 10.2337/db17-0803 PMID: 29167189
  143. Zhang, W.; Wang, Y.; Kong, Y.J.I.O. Exosomes derived from mesenchymal stem cells modulate miR-126 to ameliorate hyperglycemia-induced retinal inflammation via targeting HMGB1. Invest. Ophthalmol. Vis. Sci., 2019, 60(1), 294-303.
  144. Li, W.; Jin, L.; Cui, Y. Bone marrow mesenchymal stem cells-induced exosomal microRNA-486-3p protects against diabetic retinopathy through TLR4/NF-κB axis repression. J. Endocrinol. Invest., 2021, 44(6), 1193-1207.
  145. Safwat, A.; Sabry, D.; Ragiae, A. Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits. J. Circ. Biomark., 2018, 7, 1849454418807827.
  146. Cao, X.; Xue, L.D.; Di, Y.; Li, T.; Tian, Y.J.; Song, Y. MSC-derived exosomal lncRNA SNHG7 suppresses endothelial-mesenchymal transition and tube formation in diabetic retinopathy via miR-34a-5p/XBP1 axis. Life Sci., 2021, 272, 119232. doi: 10.1016/j.lfs.2021.119232 PMID: 33600866
  147. Sun, F.; Sun, Y.; Zhu, J. Mesenchymal stem cells-derived small extracellular vesicles alleviate diabetic retinopathy by delivering NEDD4. Stem Cell Res. Ther., 2022, 13(1), 293. doi: 10.1186/s13287-022-02983-0 PMID: 35841055
  148. Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
  149. Clinicaltrialsgov 2022. Available From: https://www.clinicaltrials.gov/ (Accessed 24 October 2022).
  150. Abdelrahman, S.; Samak, M.; Shalaby, S.J.C. Fluoxetine pretreatment enhances neurogenic, angiogenic and immunomodulatory effects of MSCs on experimentally induced diabetic neuropathy. Cell Tissue Res., 2018, 374(1), 83-97.
  151. Luo, R.; Li, L.; Liu, X. Mesenchymal stem cells alleviate palmitic acid-induced endothelial-to-mesenchymal transition by suppressing endoplasmic reticulum stress. Am. J. Physiol. Endocrinol. Metab., 2020, 319(6), 961-980.
  152. Fan, B.; Li, C.; Szalad, A. Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes. Diabetologia, 2020, 63(2), 431-433.

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