• Cecelia C Yates, Melanie Rodrigues, Austin Nuschke, Zariel I Johnson, Diana Whaley, Donna Stolz, Joseph Newsome, and Alan Wells.
• Department of Pathology, University of Pittsburgh, 3550 Terrace St., Scaife Hall, S-713, Pittsburgh, PA, 15261, USA. cey4@pitt.edu.
• Stem Cell Res Ther. 2017 Sep 5; 8 (1): 193.

BackgroundTransplantation of mesenchymal stem cells (MSC) has been proposed to improve wound healing. However, as these cells only transiently survive in the implantation site, the mechanisms underlying this beneficial healing response are associated with restorative paracrine effects of MSC matricellular factors on resident stromal cells. However, this requires that the recipient has a robust reservoir of viable cells. Here, we examine the influence of MSCs on the behavior of cotransplanted fibroblasts, in a manner to provide augmented cellular reserve to debilitated individuals, specifically focusing on matrix remodeling following in-vivo wounding.MethodsUsing a Hylan-A dermal filler hydrogel containing collagen I and tenascin-C for delivery and increased survival of transplanted cells, we find that cotransplantation of MSCs with fibroblasts reduces scarring.ResultsTransplanted xenogeneic MSCs augmented fibroblast proliferation, migration, and extracellular matrix deposition critical for wound closure, and reduced inflammation following wounding. MSCs also corrected matrix remodeling by CXCR3-deficient fibroblasts which otherwise led to hypertrophic scarring. This effect was superior to MSC or fibroblast transplantation alone.ConclusionsTaken together, these data suggest that MSCs, even if eventually rejected, transplanted with fibroblasts normalize matrix regeneration during healing. The current study provides insight into cellular therapies as a viable method for antifibrotic treatment and demonstrates that even transiently engrafted cells can have a long-term impact via matrix modulation and education of other tissue cells.

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