Regenerative Potential of Mesenchymal Stromal Cells: Age‐Related Changes

Abstract

Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult's BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult's BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

“…We conclude that PDLSCs from individuals of different age groups impart strong immunosuppressive effects on the proliferation of allogeneic PBMCs, whether in cell-cell contact culture or Transwell cultures, whereas the immunosuppressive effect of PDLSCs from adult individuals was weaker than that of PDLSCs from young subjects. These ndings agree with the results of previous reports using other kinds of MSCs, i.e., donor age in uences immunoregulation in MSCs (14,33,34), although MSC inhibition of T cell proliferation is preserved in the elderly (35). Furthermore, we found that the difference in immunosuppressive ability between APDLSCs and YPDLSCs is not related to the apoptosis of PBMCs.…”

The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice

“…These studies indicate that wounds treated with MSCs show a qualitative improvement in histological characteristics. Specifically, they report superior rete ridge architecture, multi-layered structure, improved dermal-epidermal junction and the formation of new skin appendage structures, such as hair follicles and sebaceous glands [ 22 – 26 ].…”

Function and Therapeutic Potential of Mesenchymal Stem Cells and Their Acellular Derivatives on Non-Healing Chronic Skin Ulcers

“…In fact, Arango et al conducted a study to elucidate the role of MSC acellular derivatives on wound healing using different animal models, in particular, a diabetic mouse model. The results revealed that the wounds treated with the derivatives improved the synthesis, deposition and organization of collagen fibers at the dermal matrix, relative to the wounds treated with MSCs only [124,176]. Another recent study showed that the intravenous injection of acellular derivatives promoted cutaneous wound repair when exosomes secreted by human AD-MSCs (AD-Exos) were administered in murine incisional wounds.…”