Placenta Derived Stem Cells for Treating of Chronic Ulcers and Neuropathy

Summary

This is an initial dose escalation safety and exploratory efficacy study to treat two groups of subjects with critically sized diabetic wounds and diabetic neuropathy using placental-derived stem cells (PDSC) transplanted by injection into soft tissues of the lower limb. Its primary objective is safety assessment and its secondary objective is determining optimum PDSC safe dose. Group 1 will receive implantation of cells in the ulcer, in the ulcer bed, and along the distal arterial vessels that supply blood to the foot. Group 2 will follow the same protocol for the foot but will have an additional dose of cells implanted in the anterior and posterior compartments of the same leg to determine the impact on peripheral neuropathy. Dose escalation and safety will be documented. Exploratory measures of efficacy include: ulcer healing, hemodynamic and anatomical effects on the arteries of the foot, and changes in the sensory perceptions of the foot.

Timeline

Start

2021-10-08

Primary completion

2024-03-31

Completion

2024-03-31

Publications

• Background Amos PJ, Shang H, Bailey AM, Taylor A, Katz AJ, Peirce SM. IFATS collection: The role of human adipose-derived stromal cells in inflammatory microvascular remodeling and evidence of a perivascular phenotype. Stem Cells. 2008 Oct;26(10):2682-90. doi: 10.1634/stemcells.2008-0030. Epub 2008 Apr 24.
• Background Armulik A, Genove G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011 Aug 16;21(2):193-215. doi: 10.1016/j.devcel.2011.07.001.
• Background Arnberg F, Lundberg J, Olsson A, Samen E, Jaff N, Jussing E, Dahlen U, Nava S, Axelsson R, Ringden O, Kaipe H, Holmin S. Intra-arterial Administration of Placenta-Derived Decidual Stromal Cells to the Superior Mesenteric Artery in the Rabbit: Distribution of Cells, Feasibility, and Safety. Cell Transplant. 2016;25(2):401-10. doi: 10.3727/096368915X688191. Epub 2015 May 13.
• Background Bainbridge DR, Ellis SA, Sargent IL. HLA-G suppresses proliferation of CD4(+) T-lymphocytes. J Reprod Immunol. 2000 Aug;48(1):17-26. doi: 10.1016/s0165-0378(00)00070-x.
• Background Berishvili E, Kaiser L, Cohen M, Berney T, Scholz H, Floisand Y, Mattsson J. Treatment of COVID-19 Pneumonia: the Case for Placenta-derived Cell Therapy. Stem Cell Rev Rep. 2021 Feb;17(1):63-70. doi: 10.1007/s12015-020-10004-x.
• Background Bishop PD, Feiten LE, Ouriel K, Nassoiy SP, Pavkov ML, Clair DG, Kashyap VS. Arterial calcification increases in distal arteries in patients with peripheral arterial disease. Ann Vasc Surg. 2008 Nov;22(6):799-805. doi: 10.1016/j.avsg.2008.04.008. Epub 2008 Jul 21.
• Background Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013 Jun;15(6):641-8. doi: 10.1016/j.jcyt.2013.02.006. Epub 2013 Apr 6.
• Background Bura A, Planat-Benard V, Bourin P, Silvestre JS, Gross F, Grolleau JL, Saint-Lebese B, Peyrafitte JA, Fleury S, Gadelorge M, Taurand M, Dupuis-Coronas S, Leobon B, Casteilla L. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia. Cytotherapy. 2014 Feb;16(2):245-57. doi: 10.1016/j.jcyt.2013.11.011.
• Background Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011 Jul 8;9(1):11-5. doi: 10.1016/j.stem.2011.06.008.
• Background Carstens MH, Correa D, Llull R, Gomez A, Turner E, Valladares S. Subcutanous reconstruction of hand dorsum for late sequelae of burn scars using stromal vascular fractions (SVF). CellR4 2015; 3; e1675.
• Background Carstens MH, Gomez A, Cortes R, Turner E, Perez C, Ocon M, Correa D. Non-reconstructable peripheral vascular disease of the lower extremity in ten patients treated with adipose-derived stromal vascular fraction cells. Stem Cell Res. 2017 Jan;18:14-21. doi: 10.1016/j.scr.2016.12.001. Epub 2016 Dec 8.
• Background Carstens MH, Mendieta M, Perez C, Villareal E, Garcia R. Assisted Salvage of Ischemic Fasciocutaneous Flap Using Adipose-Derived Mesenchymal Stem Cells: In-Situ Revascularization. Aesthet Surg J. 2017 Jul 1;37(suppl_3):S38-S45. doi: 10.1093/asj/sjx052.
• Background Carstens MH, Pérez M, Briceño H, Valladares S, Correa D. Treatment of late sequelae of burn scar fibrosis with adipose-derived stromal vascular fraction (SVF) cells: a case series. CellR4 2017; 5: e2404.

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Indications