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Bone Marrow-MSCs: The Magic Ingredient for Enhanced Irradiation Injury Wound Repair?

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Review of “Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs” from STEM CELLS Translational Medicine by Stuart P. Atkinson

The exposure of the skin to ionizing radiation, and the subsequent massive inflammatory response, leads to skin necrosis, ulceration, and fibrosis [1]. Various surgical approaches can promote wound healing, although the scar remains fragile and unstable. The anti-inflammatory and pro-regenerative characteristics of mesenchymal stem cells (MSCs) has led to their application during surgical interventions for severe radiological syndrome [2], although most MSC-based studies have tended to concentrate on short-term analyses [3] with the longer term consequences left relatively unstudied. 

However, a new STEM CELLS Translational Medicine study from the laboratory of Christine Linard (Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France) now reports on the long-term effects of bone marrow (BM)-MSC treatment on wound-healing after surgery to treat cutaneous radiation overexposure [4].

Linard et al. compared wound healing after irradiation overexposure to the rump of the minipig model in three different scenarios; i) vascularized-flap surgery and local autologous BM-MSC injections alongside three additional weekly doses of BM-MSCs, ii) surgery alone, and iii) simple excision of necrotic tissue. The study employed minipigs given their acceptance as a preferred animal model for human skin wounds [5].

After one year, the simple excision of necrotic tissue led to the failure of the remodeling/resolution phase of wound healing, leading to fibroblastic activation, excess extracellular matrix (ECM) production, and significant hypertrophic scarring. Vascularized-flap surgery also displayed signs of inadequate wound remodeling and healing, including low ECM production and subsequent matrix immaturity, persistent inflammation, and loss of vascularization. However, the addition of BM-MSCs significantly enhanced vascularized-flap surgery, leading to enhanced wound remodeling and healing, low inflammation, and stable vascularization, probably via the stabilization of fibroblast activation and ECM protein expression.

Overall, BM-MSCs seem to represent the “magic ingredient” that promotes successful irradiation injury wound repair via vascularized flap surgery in a large-animal model, with a singular importance noted for proper ECM synthesis.

For more on how stem cells can aid wound healing, stay tuned to the Stem Cells Portal!

References

  1. Zhao W and Robbins ME, Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem 2009;16:130-43.
  2. Benderitter M, Gourmelon P, Bey E, et al., New emerging concepts in the medical management of local radiation injury. Health Phys 2010;98:851-7.
  3. Zhang J, Huang X, Wang H, et al., The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy. Stem Cell Research & Therapy 2015;6:234.
  4. Linard C, Brachet M, Strup-Perrot C, et al., Autologous Bone Marrow Mesenchymal Stem Cells Improve the Quality and Stability of Vascularized Flap Surgery of Irradiated Skin in Pigs. STEM CELLS Translational Medicine 2018;7:569-582.
  5. Swindle MM, Makin A, Herron AJ, et al., Swine as Models in Biomedical Research and Toxicology Testing. Veterinary Pathology 2012;49:344-356.