Mesenchymals for wound healing
Nara Medical University, Japan -
Mesenchymal stem cells are classically defined as CD34 negative, CD45 negative, SH2 and SH4 positive, and Thy-1 (CD90) positive cells. Therapeutically mesenchymal stem cells are attractive because they do not require matching with recipients, supposedly because mesenchymal stem cells are immune modulatory". Osiris Therapeutics not only holds some of the key patents on mesenchymal stem cell composition of matter but also patents on allogeneic uses of mesenchymal stem cells. Interestingly it is also Osiris that demonstrated intravenously delivered mesenchymal stem cells help patients with heart failure. Given the regenerative, immune modulatory, and immune privileged properties of mesenchymal stem cells, one exciting possible use for these cells would be in acceleration of wound healing. In a recent paper (Yoshikawa et al. Wound therapy by marrow mesenchymal cell transplantation. Plast Reconstr Surg. 2008 Mar;121(3):860-77) this is exactly what was performed.
The authors derived bone marrow mesenchymal stem cells from a donor and cultured them, and placed the cells on a collagen sponge in order to mimick an artificial dermis layer. In order to test bioactivity of this "graft" the authors implanted it subcutaneously into an immune compromised mouse and explanted it after ten days. Histological examination of the implant demonstrated differentiation of the human marrow mesenchymal cells into dermal tissue.
The next step the authors wanted to see if this collagen-MSC mixture may be of therapeutic value.
Twenty patients with treatment refractory dermatopathies were selected and autologous "grafts" were generated using bone marrow mesenchymal stem cells and collagen matrix. This graft was placed on the wound areas. In 18 of the 20 patients improvements in the previous non-healing wounds was demonstrated.
These data make one ask the question why allogeneic "off the shelf" products for this indication are not already on the market.
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Prof. Dr. Eduardo Mansilla MD said...
Comment from Prof. Dr. Eduardo Mansilla MD
Tissue Engineering, Regenerative Medicine and Cell Therapies Laboratory
CUCAIBA
La Plata
Argentina
You will probably find more data and ideas about this topic in these
papers published by our group.
Human mesenchymal stem cells are tolerized by mice and improve skin
and spinal cord injuries.Transplant Proc. 2005 Jan-Feb;37(1):292-4.
Mansilla E, Marin GH, Sturla F, Drago HE, Gil MA, Salas E, Gardiner
MC, Piccinelli G, Bossi S, Salas E, Petrelli L, Iorio G, Ramos CA,
Soratti C.
Bloodstream cells phenotypically identical to human mesenchymal bone
marrow stem cells circulate in large amounts under the influence of
acute large skin damage: new evidence for their use in regenerative
medicine.Transplant Proc. 2006 Apr;38(3):967-9.
Mansilla E, Marín GH, Drago H, Sturla F, Salas E, Gardiner C, Bossi S,
Lamonega R, Guzmán A, Nuñez A, Gil MA, Piccinelli G, Ibar R, Soratti C.
Mesenchymal stem cells, could they be the link between tolerance and
regeneration?
Burns. 2007 Mar;33(2):137-8.
Mansilla E, Drago H, Marin GH, Sturla F, Ibar R, Soratti C.
Matrix superhighways configurations: new concepts for complex organ
regeneration.
Transplant Proc. 2007 Sep;39(7):2431-3.
Mansilla E, Drago H, Sturla F, Bossi S, Salas E, Marín GH, Ibar R, Soratti C.