Transplantation of decellularised human amniotic membranes seeded with mesenchymal stem cell‐educated macrophages into animal models

Abstract

The reconstruction of chronic skin wounds remains a public health challenge in dermatology. Precisely controlling and monitoring the wound-healing process should result in enhanced outcomes for the patient. Cell-based therapies have shown great potential in medicine due to their immunomodulatory and healing properties. Herein, we produced activated macrophages by treating circulating monocytes with mesenchymal stem cell (MSC) supernatant. We also demonstrated the critical role of activated macrophages transplantation using amniotic membranes in accelerating wound healing in an animal wound model. The activated macrophages not only exhibited immunomodulatory cytokines like transforming growth factorβ (TGFβ) and interleukin 10 (and IL10) secretion but also showed attachment and proliferation ability on the amniotic membrane scaffold. Moreover, MSCs supernatant-treated cells also displayed significant ARG1, CD206, and IL 10 genes expression. Inspired by the in vitro results, we examined the in vivo therapeutic efficacy of the activated macrophage transplantation using an acellular amniotic membrane carrier in a full-thickness cutaneous wound model. The wound healing rate was significant in the group treated with macrophages generated via mesenchymal cell therapy seeded human amniotic membrane. There was less scarring in the wound sites after placing cell-scaffold constructs in the wound sites in the animal models. Overall, macrophages stimulated with mesenchymal cells' supernatant exhibited improved healing processes in incisional wounds by decreasing the inflammatory phase, increasing angiogenesis, and reducing scar tissue development.

Immune response: the Achilles’ heel of the stem cell-based regenerative therapies

“…Functionally, these macrophages cocultured with MSCs showed a higher level of phagocytic activity and polarization to the M2 phenotype. Using three-dimensional (3D) models, a gelatin methacryloyl (GelMA) hydrogel encapsulating BM-MSCs and macrophages showed optimal effects on the proliferation, migration, osteogenic and chondrogenic differentiation, while also showing significant M2 macrophage polarization [55]. Inspired by these in vitro results, the in vivo implantation of hydrogels promoted osteochondral repair through an intrinsic crosstalk between MSCs and macrophages at the bone injury.…”

The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration

“…Amino-functionalized mesoporous silica nanoparticles (MSNs) can enhance the stability of hydrogel beads and significantly improve the proliferative properties of human adipose-derived mesenchymal stem cells (hASCs). In one study, treating circulating monocytes with mesenchymal stem cell (MSC) superserum to produce activated macrophages in a double-layer scaffold composed of hydrogels and nanofibers resulted in faster wound healing rates [119]. In another similar study, a double-layer scaffold composed of hydrogels and nanofibers was also prepared, and ADSCs were inoculated onto it; the optimal performance of re-epithelialization, collagen tissue production, neovascularization, and reduction in inflammation in the wound area were observed [120].…”