Matrigel scaffold, alone or with human placenta-derived mesenchymal stromal cells, improves histological repair of murine excisional wounds

Impaired cutaneous wound healing remains a major clinical challenge, particularly when excessive inflammation disrupts tissue regeneration and extracellular matrix remodeling. Mesenchymal stromal cells (MSCs; the term recommended by the International Society for Cell & Gene Therapy in preference to “mesenchymal stem cells”) have been proposed as therapeutic agents on the basis of their immunomodulatory and paracrine properties. Human placenta-derived mesenchymal stromal cells (hPMSCs) are of particular interest because of their accessibility, proliferative capacity and low reported immunogenicity. Whether their benefit in cutaneous wounds is attributable to the cells themselves, to the delivery vehicle, or to both, has not been resolved. In this preclinical study, two full-thickness excisional wounds were created on the dorsum of female BALB/c mice and treated by intradermal injection with hPMSCs alone, hPMSCs incorporated within a Matrigel scaffold, Matrigel alone, or vehicle (DMEM) control. Separate cohorts were euthanized on days 7, 14 and 21 post-wounding ( n = 5 mice, 10 wounds, per group per time point). Wound repair was assessed by histological and histomorphometric analysis of haematoxylin and eosin and Masson’s trichrome-stained sections. Collagen density was quantified morphometrically from Masson’s trichrome-stained sections, and re-epithelialization was graded on a five-point ordinal scale. Inflammatory cell infiltration and skin appendage regeneration were described qualitatively and were not quantified; inflammatory cells were not counted, and serial macroscopic wound-area measurements were not performed. Serum interleukin-10 (IL-10), interleukin-17 (IL-17) and interferon-γ (IFN-γ) were measured by ELISA on days 7, 14 and 21 as indices of the systemic inflammatory response. All three treatments improved histological repair relative to vehicle control. At day 21, collagen density was 86.1 ± 7.5% in the hPMSC + Matrigel group, compared with 77.8 ± 6.6% for Matrigel alone, 68.4 ± 5.1% for hPMSCs alone and 45.1 ± 4.1% for vehicle control. Across the three time points, the improvement in collagen density observed with Matrigel alone was 80–93% as large as the combination-versus-vehicle difference when the group means were compared descriptively. Adding hPMSCs to the scaffold gave a modest further increase of 5.8, 3.8 and 8.3% points at days 7, 14 and 21, which remained significant after Bonferroni adjustment only at day 7. The combination showed the highest re-epithelialization grade and the most organized dermal architecture on qualitative histological assessment at day 21. Systemically, hPMSC administration was associated with elevated serum IL-10 and reduced IFN-γ relative to control, with little difference in IL-17. In this model, a Matrigel scaffold improved histological wound repair relative to vehicle; adding hPMSCs to the scaffold gave a modest further increase in collagen density, and the combination performed best of the conditions tested. Because the study includes no non-MSC cellular control, the incremental benefit of the cells over the scaffold cannot be attributed specifically to hPMSC identity; and because no local (wound-bed) immunological or angiogenic analysis was performed, the accompanying serum cytokine changes represent a systemic association rather than a demonstrated local immunomodulatory mechanism. These findings should be regarded as an initial preclinical observation supporting combined cell–scaffold delivery, which requires confirmation with an appropriate cellular control and direct assessment of the wound microenvironment.