The State of Mesenchymal Stem Cell Therapies to Accelerate Regeneration

Therapies using mesenchymal stem cells are quite widely used at the present time, but efficacy varies considerably, clinic by clinic, even between those groups ostensibly taking exactly the same approach to cell source and methodologies of treatment. Working with cells isn't easy, and very small differences in protocol can lead to large differences in the behavior and type of cells that result. The majority of such treatments see transplanted cells die quite quickly, but their signaling produces effects on native cell behavior. Suppression of chronic inflammation is the most consistent outcome, but improvements in regeneration, or in functional capacity in older people, are harder to obtain with any great reliability. Some groups claim to be able to make transplanted mesenchymal stem cells engraft and survive in large enough numbers to make a difference, but this isn't common. Thus this is a field of medicine in which there remains considerable room for improvement.

Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process.

During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing.

The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. ADSCs fulfill the general accepted criteria for cell-based therapies, but nonetheless still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.