Effectiveness of Secretome from Human Umbilical Cord Mesenchymal Stem Cells in Gel (10% SM-hUCMSC Gel) for Chronic Wounds (Diabetic and Trophic Ulcer) – Phase 2 Clinical Trial

References

• Werdin F, Tennenhaus M, Schaller H-E, Rennekampff H-O. Evidence-based management strategies for treatment of chronic wounds. Eplasty. 2009;9:25.
   Google Scholar
• Cazander G, Pritchard DI, Nigam Y, Jung W, Nibbering PH. Multiple actions of Lucilia sericata larvae in hard-to-heal wounds. BioEssays. 2013;35(12):1083–1092. doi:10.1002/bies.201300071
   PubMed Web of Science ®Google Scholar
• Robson MC, Barbul A. Guidelines for the best care of chronic wounds. Wound Repair Regen. 2006;14(6):647–648. doi:10.1111/j.1524-475X.2006.00173.x
   PubMed Web of Science ®Google Scholar
• Gottrup F. A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am J Surg. 2004;187(5):S38–S43. doi:10.1016/S0002-9610(03)00303-9
   Google Scholar
• Wicke C, Bachinger A, Coerper S, Beckert S, Witte MB, Königsrainer A. Aging influences wound healing in patients with chronic lower extremity wounds treated in a specialized wound care center. Wound Repair Regen. 2009;17(1):25–33. doi:10.1111/j.1524-475X.2008.00438.x
   PubMed Web of Science ®Google Scholar
• Järbrink K, Ni G, Sönnergren H, et al. Prevalence and incidence of chronic wounds and related complications: a protocol for a systematic review. Syst Rev. 2016;5(1). doi:10.1186/s13643-016-0329-y.
   PubMedGoogle Scholar
• Jöster M, Kröger K. Prevalence of chronic wounds in different modalities of care in Germany. Eur WOUND Manag Assoc J. 2018;2018:75.
   Google Scholar
• Macdonald J. Global Initiative for Wound and Lymphoedema Care (GIWLC). Wounds UK. 2009;4:92–95.
   Google Scholar
• Denny K, Lawand C, Perry SD. Compromised wounds in Canada. Health Q. 2014;17(1):7–10. doi:10.12927/hcq.2014.23787
   PubMedGoogle Scholar
• Ragnarson Tennvall G, Apelqvist J. Health-economic consequences of diabetic foot lesions. Clin Infect Dis. 2004;39(Supplement_2):S132–S139. doi:10.1086/383275
   PubMedGoogle Scholar
• Rice JB, Desai U, Cummings AKG, Birnbaum HG, Skornicki M, Parsons NB. Burden of diabetic foot ulcers for medicare and private insurers. Diabetes Care. 2014;37(3):651–658. doi:10.2337/dc13-2176
   PubMed Web of Science ®Google Scholar
• Jeffcoate W, Bakker K. World diabetes day: footing the bill. Lancet. 2005;365(9470):1527. doi:10.1016/S0140-6736(05)66437-9
   PubMed Web of Science ®Google Scholar
• Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Ann Med. 2017;49(2):106–116. doi:10.1080/07853890.2016.1231932
   PubMed Web of Science ®Google Scholar
• UNAIDS. Global AIDS Update 2016. World Health Organization; 2016.
   Google Scholar
• World Health Organization. Global Leprosy Strategy 2016–2020. World Health Organization; 2016.
   Google Scholar
• World Health Organization. Global leprosy update, 2016: accelerating reduction of disease burden. Relev Epidemiol Hebd. 2017;92(35):501–519.
   PubMedGoogle Scholar
• Kemenkes RI. Data dan Informasi profil Kesehatan Indonesia 2018 [Ministry of Health of the Republic of Indonesia]. Data dan Inf Profil Kesehat Indones; 2018.
   Google Scholar
• Yolanda MM. Adult stem cell therapy in chronic wound healing. J Stem Cell Res Ther. 2014;04(01). doi:10.4172/2157-7633.1000162
   Google Scholar
• Bluestein D, Javaheri A. Pressure ulcers: prevention, evaluation, and management. Am Fam Physician. 2008;78(10):1186–1194.
   PubMed Web of Science ®Google Scholar
• Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–317. doi:10.1080/14653240600855905
   PubMed Web of Science ®Google Scholar
• Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–4295. doi:10.1091/mbc.e02-02-0105
   PubMed Web of Science ®Google Scholar
• Qomi RT, Sheykhhasan M. Adipose-derived stromal cell in regenerative medicine: a review. World J Stem Cells. 2017;9(8):107. doi:10.4252/wjsc.v9.i8.107
   PubMed Web of Science ®Google Scholar
• Zollino I, Zuolo M, Gianesini S, et al. Autologous adipose-derived stem cells: basic science, technique, and rationale for application in ulcer and wound healing. Phlebology. 2017;32(3):160–171. doi:10.1177/0268355516641546
   PubMed Web of Science ®Google Scholar
• Singh R, Singh R, Rohilla RK, Siwach R, Verma V, Kaur K. Surgery for pressure ulcers improves general health and quality of life in patients with spinal cord injury. J Spinal Cord Med. 2010;33(4):396–400. doi:10.1080/10790268.2010.11689718
   PubMed Web of Science ®Google Scholar
• Sorrell JM, Caplan AI. Topical delivery of mesenchymal stem cells and their function in wounds. Stem Cell Res Ther. 2010;1(4). doi:10.1186/scrt30
   PubMedGoogle Scholar
• Utomo W, Dewi YI, Abdurrasyid T. Efektifitas nigella sativa oil untuk mencegah terjadinya ulkus dekubitus pada pasien tirah baring lama [Effectiveness of nigella sativa oil to prevent decubitus ulcers in long bed rest patients]. J Ners Indones. 2014;2(2):151–157.
   Google Scholar
• González Sarasúa J, Pérez López S, Viejo M Á, et al. Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury. J Spinal Cord Med. 2011;34:301.
   PubMed Web of Science ®Google Scholar
• Damayanti RH, Rusdiana T, Wathoni N. Mesenchymal stem cell secretome for dermatology application: a review. Clin Cosmet Investig Dermatol. 2021;14:1401–1412. doi:10.2147/CCID.S331044
   PubMed Web of Science ®Google Scholar
• Silveira BM, Ribeiro TO, Freitas RS, et al. Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair. PLoS One. 2022;17(12):e0277863. doi:10.1371/journal.pone.0277863
   PubMed Web of Science ®Google Scholar
• Park S-R, Kim J-W, Jun H-S, Roh JY, Lee H-Y, Hong I-S. Stem cell secretome and its effect on cellular mechanisms relevant to wound healing. Mol Ther. 2018;26(2):606–617. doi:10.1016/j.ymthe.2017.09.023
   PubMed Web of Science ®Google Scholar
• Cunningham CJ, Redondo-Castro E, Allan SM. The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke. J Cereb Blood Flow Metab. 2018;38(8):1276–1292. doi:10.1177/0271678X18776802
   PubMed Web of Science ®Google Scholar
• Ahangar P, Mills SJ, Cowin AJ. Mesenchymal stem cell secretome as an emerging cell-free alternative for improving wound repair. Int J Mol Sci. 2020;21(19):7038. doi:10.3390/ijms21197038
   PubMed Web of Science ®Google Scholar
• Wang M, Xu X, Lei X, Tan J, Xie H. Mesenchymal stem cell-based therapy for burn wound healing. Burn Trauma. 2021;9. doi:10.1093/burnst/tkab002/6261432:
   Web of Science ®Google Scholar
• Zriek F, Di Battista JA, Alaaeddine N. Mesenchymal stromal cell secretome: immunomodulation, tissue repair and effects on neurodegenerative conditions. Curr Stem Cell Res Ther. 2021;16(6):656–669. doi:10.2174/1574888X16666210202145639.
   PubMed Web of Science ®Google Scholar
• De Kock J, Rodrigues RM, Branson S, et al. Inflammation alters the secretome and immunomodulatory properties of human skin-derived precursor. Cells. 2020;9(4):914. doi:10.3390/cells9040914
   PubMed Web of Science ®Google Scholar
• Colombini A, Libonati F, Lopa S, et al. Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: from predictive fiction toward reality. Front Med. 2022;9. doi:10.3389/fmed.2022.992386.
   Web of Science ®Google Scholar
• Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther. 2016;7(1):1–13. doi:10.1186/s13287-016-0363-7
   PubMedGoogle Scholar
• English K. Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol. 2013;91(1):19–26. doi:10.1038/icb.2012.56
   PubMed Web of Science ®Google Scholar
• Liang X, Ding Y, Zhang Y, Tse HF, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2014;23(9):1045–1059. doi:10.3727/096368913X667709
   PubMed Web of Science ®Google Scholar
• Patel DM, Shah J, Srivastava AS. Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem Cells Int. 2013;2013:1–15. doi:10.1155/2013/496218
   Web of Science ®Google Scholar
• Fu Y, Karbaat L, Wu L, Leijten J, Both SK, Karperien M. Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Eng Part B Rev. 2017;23(6):515–528. doi:10.1089/ten.teb.2016.0365
   PubMed Web of Science ®Google Scholar
• Vizoso F, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18(9):1852. doi:10.3390/ijms18091852
   PubMed Web of Science ®Google Scholar
• Jeon YK, Jang YH, Yoo DR, Kim SN, Lee SK, Nam MJ. Mesenchymal stem cells’ interaction with skin: wound-healing effect on fibroblast cells and skin tissue. Wound Repair Regen. 2010;18(6):655–661. doi:10.1111/j.1524-475X.2010.00636.x
   PubMed Web of Science ®Google Scholar
• Bronckaers A, Hilkens P, Martens W, et al. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol Ther. 2014;143(2):181–196. doi:10.1016/j.pharmthera.2014.02.013
   PubMed Web of Science ®Google Scholar
• Elman JS, Murray RM, Wang F, et al. Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. PLoS One. 2014;9(2):e89882. doi:10.1371/journal.pone.0089882
   PubMed Web of Science ®Google Scholar
• van Rhijn-Brouwer FCC, Gremmels H, Fledderus JO, et al. A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol. BMJ Open. 2018;8(8):e020479. doi:10.1136/bmjopen-2017-020479
   PubMed Web of Science ®Google Scholar
• Sinno H, Prakash S. Complements and the Wound Healing Cascade: an Updated Review. Plast Surg Int. 2013;2013:1–7. doi:10.1155/2013/146764
   Google Scholar
• Samakova A, Gazova A, Sabova N, Valaskova S, Jurikova M, Kyselovic J. The pi3k/Akt pathway is associated with angiogenesis, oxidative stress and survival of mesenchymal stem cells in pathophysiologic condition in ischemia. Physiol Res. 2019;S131–S138. doi:10.33549/physiolres.934345
   PubMed Web of Science ®Google Scholar
• Cerqueira MT, Pirraco RP, Marques AP. Stem cells in skin wound healing: are we there yet? Adv Wound Care. 2016;5(4):164–175. doi:10.1089/wound.2014.0607
   PubMed Web of Science ®Google Scholar
• Ojeh NO, Navsaria HA. An in vitro skin model to study the effect of mesenchymal stem cells in wound healing and epidermal regeneration. J Biomed Mater Res Part A. 2014;102(8):2785–2792. doi:10.1002/jbm.a.34950
   PubMed Web of Science ®Google Scholar
• Lee SH, Jin SY, Song JS, Seo KK, Cho KH. Paracrine effects of adipose-derived stem cells on keratinocytes and dermal fibroblasts. Ann Dermatol. 2012;24(2):136. doi:10.5021/ad.2012.24.2.136
   PubMed Web of Science ®Google Scholar
• Park BS, Jang KA, Sung JH, et al. Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging. Dermatologic Surg. 2008;34:1323.
   PubMed Web of Science ®Google Scholar
• Jin HJ, Bae YK, Kim M, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci. 2013;14(9):17986–18001. doi:10.3390/ijms140917986
   PubMed Web of Science ®Google Scholar
• Stoff A, Rivera AA, Banerjee NS, et al. Promotion of incisional wound repair by human mesenchymal stem cell transplantation. Exp Dermatol. 2009;18(4):362–369. doi:10.1111/j.1600-0625.2008.00792.x
   PubMed Web of Science ®Google Scholar