Stem Cells in Wound Care
Stem cells have been a consistent hot topic of discussion within the scope of regenerative medicine for some time now. As it relates to wound healing, there are 3 primary types of stem cells that have demonstrated an innate ability to facilitate closure of a wound. Those types of stem cells being epidermal and dermal stem cells, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and hematopoietic stem cells (HSCs). Each respective cell type has a varying degree of potency, quantity, and accessibility.
Of these cell types, MSCs are often the front runner for usage in regenerative therapies. These cells can be derived from multiple locations including the umbilical cord and the umbilical cord blood & placenta in fetal tissue and can be derived from both bone marrow and adipose tissue in the adult body.
“During wound healing, MSCs take part in all stages of this process and were proven to persist at the wound site even after the completion of healing (Pratheesh et al., 2017). They coordinate the inflammatory process, modulate fibrosis and reduce scarring, as they show strong immunomodulatory and immunoregulatory characteristics demonstrated by release of cytokines, chemokines and growth factors (Hu et al., 2014; Mester et al., 2017; Ren et al., 2008). It is reported, that human MSCs release over 30 biomolecules, that promote wound healing (Hwang et al., 2009). Thus, they not only coordinate inflammation, fibrosis and scarring, but also increase angiogenesis and granulation tissue formation (Maxson et al., 2012), show antimicrobial activity (Krasnodembskaya et al., 2010), neutralize reactive oxygen species (ROS) (Sato et al., 2007) and enhance dermal fibroblast function (Smith et al., 2010). Moreover, it was shown, that MSCs conditioned medium (via paracrine signaling) stimulates stem cells residing near the damaged tissue to repair the defect (Ho et al., 2018)” (Kucharzewskia et al, 2019).
There is a degree of comfort that comes with utilizing MSCs as their mechanism of action is well-known. “They are able to differentiate and transdifferentiate into tissue specific cells, to secrete a wide range of paracrine factors, to regulate immune response and local tissue microenvironment (Li and Fu, 2012)” (Kucharzewskia et al, 2019).
One of the leading difficulties in the administration of stem cell therapies to non-healing wounds comes from limitations in delivery methods. The simplest of those methods includes direct topical application or injection directly into the dermis. “…these methods have many limitations, for example difficulties in tissue targeting and high cell attrition rate (in the case of systemic delivery), low cell survival, additional tissue damages, lack of cell-ECM attachment and hostile wound environment (in the case of local administration)” (Kucharzewskia et al, 2019). Because of this, bioscaffold-based methods of delivery (skin-substitutes) have come into the spotlight. “These biomaterials are commonly used for stem cell delivery into the wound difficult to heal, as they show high biocompatibility, bioactivity and biodegradability (Kohane and Langer, 2008)” (Kucharzewskia et al, 2019).
The efficacy of stem cells as it relates to wound healing is drawn primarily from their paracrine activity in the modulation, production, and secretion of bio-molecules such as growth factors and cytokines. In a chronic wound environment, these types of molecules are often present in a deficit, leading to wounds becoming stalled in either the inflammatory phase, or early stages of the proliferative phase of healing. These cells not only differentiate and proliferate, but also can promote the cells in vivo for migration, immunomodulation and angiogenesis. These properties of stem cells, MSCs in particular, have made them a favorable method of treatment for non-healing, chronic wounds. With continued research into the mechanism of action of varying stem cell types, along with bio-compatible scaffolds, advances in this realm of regenerative medicine can continue to be made.
In my conversations with providers in the field, the topic of stem cells often comes up. I always find their justifications for therapies to be interesting because there is so much variability from one provider to the next. Some justifications are very specific, discussing the activity of stem cells at a micro level and their effects within the wound environment, while others are vaguer simply stating that “stem cells are well studied and their success in healing wounds is well documented.” No matter how you spin it, stem cells in wound care aren’t going away. Whether you are looking for quantitative or qualitative proof that stem cells are a therapy worth using, both are abundantly available and the validity of both will only continue to improve with time.
If you enjoyed this article or have interesting insight/experiences with stem cells in wound care, please feel free to share in the comments below.
References:
Kucharzewski, Marek, et al. “Novel Trends in Application of Stem Cells in Skin Wound Healing.” European Journal of Pharmacology, vol. 843, 2019, pp. 307–315., doi:10.1016/j.ejphar.2018.12.012.
Giri, Shibashish, et al. “Therapeutic Potential of Endogenous Stem Cells and Cellular Factors for Scar-Free Skin Regeneration.” Drug Discovery Today, vol. 24, no. 1, 2019, pp. 69–84., doi:10.1016/j.drudis.2018.10.014.
Park, Se-Ra, et al. “Stem Cell Secretome and Its Effect on Cellular Mechanisms Relevant to Wound Healing.” Molecular Therapy, vol. 26, no. 2, 2018, pp. 606–617., doi:10.1016/j.ymthe.2017.09.023.
