Handling difficult wounds using Mesenchymal stem cells

Handling difficult wounds using Mesenchymal stem cells

Close to 6.5 million patients in the US suffer from chronic wounds: with a whopping cost of US$25 billion spent per year on treating chronic wounds. These numbers are on the rise given the increase in the aging population and incidences in obesity and diabetes (Sen et al, 2009).

In the case of basic wound care as well as special therapies for non-healing wounds, several approaches are sought after. These range from the use of antibiotics to compression wraps for venous ulcers to lower edema to debridement to applying negative pressure to remove the fluid. There is a certain degree of overlap between these different treatment approaches. Though the outcome may be improved, complete closure of wounds is seen to an extent of 50–60%(Otero-Viñas and Falanga, 2016).

Apart from the criteria listed by the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy, a mesenchymal stem cell (MSC) can be expanded in vitro using appropriate culture conditions. Scientists Shimizu and colleagues reported in 2008 that MSCs can transdifferentiate into multiple skin cell types in mice wounds. At the site of wounds in mice, MSCs isolated from the bone marrow differentiated into skin cells: keratinocytes, endothelial cells, and pericytes, as evidenced by the expression of relevant markers. The involvement of CCR7 was shown to be involved in the migration of MSCs. The wounds in the animals that received MSCs showed fast repair that was further augmented by the injection of SLC/CCL21: the ligand of CCR7 showing the suitability of stem cell-based therapy for efficiently healing wounds.

Another team showed the concept of MSC wound engraftment for the first time: cancer patients with acute wounds and those with long-standing, non-healing wounds were the source of a single bone marrow aspirate from which MSCs were cultured. Application of these cultured autologous MSCs was done using a fibrin polymer spray system with a double-barrelled syringe on the wounds up to four times. Post-cell application biopsies revealed the presence of elongated spindle cells that expressed MSC markers to generate elastin-responsible for forming elastic fibers. There were no adverse effects of MSC application and there was a statistically significant lowering of the wound sizes. This shows the suitability of autologous bone marrow-derived MSCs in chronic wound healing (Falanga et al, 2007).

Given that the increasing incidences and costs associated with chronic wounds (Otero-Viñas and Falanga, 2016), novel techniques are the need of the hour for wound healing. Among these approaches is the use of MSCs that have been shown to be safe and effective in wound closure in both animal models and several clinical trials. On account of the wound closure, an increase in the tensile strength within the wound, as well as the promotion of angiogenesis, to also suppress the inflammatory responses that are shown by MSCs-stem cells are the safe and efficient way forward for healing wounds.

References:

Sen, C. K., Gordillo, G. M., Roy, S., Kirsner, R., Lambert, L., Hunt, T. K., Gottrup, F., Gurtner, G. C., &Longaker, M. T. (2009). Human skin wounds: a major and snowballing threat to public health and the economy. Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society17(6), 763–771.

Otero-Viñas, M., &Falanga, V. (2016).Mesenchymal Stem Cells in Chronic Wounds: The Spectrum from Basic to Advanced Therapy. Advances in wound care5(4), 149–163.

Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D, Shimizu H. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol 2008;180:2581–2587.

Falanga V, Iwamoto S, Chartier M, et al. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Eng 2007;13:1299–1312.

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