Enhanced growth of endothelial precursor cells on PCG-matrix facilitates accelerated, fibrosis-free, wound healing: a diabetic mouse model.
Diabetes mellitus (DM)-induced endothelial progenitor cell (EPC) dysfunction causes impaired wound healing, which can be rescued by delivery of large numbers of 'normal' EPCs onto such wounds. The principal challenges herein are (a) the high number of EPCs required and (b) their sustained delivery onto the wounds. Most of the currently available scaffolds either serve as passive devices for cellular delivery or allow adherence and proliferation, but not both. This clearly indicates that matrices possessing both attributes are 'the need of the day' for efficient healing of diabetic wounds. Therefore, we developed a system that not only allows selective enrichment and expansion of EPCs, but also efficiently delivers them onto the wounds. Murine bone marrow-derived mononuclear cells (MNCs) were seeded onto a PolyCaprolactone-Gelatin (PCG) nano-fiber matrix that offers a combined advantage of strength, biocompatibility wettability; and cultured them in EGM2 to allow EPC growth. The efficacy of the PCG matrix in supporting the EPC growth and delivery was assessed by various in vitro parameters. Its efficacy in diabetic wound healing was assessed by a topical application of the PCG-EPCs onto diabetic wounds. The PCG matrix promoted a high-level attachment of EPCs and enhanced their growth, colony formation, and proliferation without compromising their viability as compared to Poly L-lactic acid (PLLA) and Vitronectin (VN), the matrix and non-matrix controls respectively. The PCG-matrix also allowed a sustained chemotactic migration of EPCs in vitro. The matrix-effected sustained delivery of EPCs onto the diabetic wounds resulted in an enhanced fibrosis-free wound healing as compared to the controls. Our data, thus, highlight the novel therapeutic potential of PCG-EPCs as a combined 'growth and delivery system' to achieve an accelerated fibrosis-free healing of dermal lesions, including diabetic wounds.
National Centre for Cell Science, NCCS Complex, University of Pune Campus, Ganeshkhind, Pune, Maharashtra, India.
Meghana
M
Kanitkar
Amit
A
Jaiswal
Rucha
R
Deshpande
Jayesh
J
Bellare
Vaijayanti P
VP
Kale
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology*; D005355:Fibrosis; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005780:Gelatin / Q000494:pharmacology*; D008297:Male; D008422:Materials Testing; D051379:Mice; D011091:Polyesters / Q000494:pharmacology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
D001672:Biocompatible Materials; D011091:Polyesters; C016240:polycaprolactone; D005780:Gelatin