Long‐term bone marrow culture and its clinical potential in chronic wound healing

Abstract

Bone marrow-derived cells have long been regarded to play a crucial role in the homeostasis of skin. We have previously described the clinical benefit of directly applying autologous bone marrow aspirate and cultured bone marrow cells to recalcitrant chronic skin wounds. The initial response to treatment appears to be vascular in nature with the formation of new blood vessels. The difficulty in consistently growing adequate numbers of cells for delivery to patients was, however, a limiting factor. Here, in a subsequent protocol, we describe an improved bone marrow culture system yielding a reliable growth of bone marrow cells and leading to a greater clinical response. Cells expressing markers of endothelial progenitors including CD133, CD146, and particularly CD14 are enhanced in these cultures. CD14-isolated cells produced colonies in endothelial cell assays and sprouting in matrigel assays. Angiogenic cytokines, including angiogenin, epithelial neutrophil-activating protein-78, growth-regulated oncogene, growth-regulated oncogene-alpha, Interleukin-8, CXC16, and monocyte chemoattractant protein-1, were found to be elevated in these cultures. Administration of improved culture cells to patients with chronic wounds present for >1 year lead to an enhanced clinical response.

Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro

“…Previous work in our laboratory has demonstrated that bone marrow-derived cells play an important role in cutaneous wound healing and that direct application of bone marrow-derived cells to patients with chronic nonhealing wounds leads to wound closure and dermal rebuilding [43][44][45][46][47].…”

Memory Encoded Throughout Our Bodies: Molecular and Cellular Basis of Tissue Regeneration

“…In clinical practice, unavoidable vascular damage is often created during actinic, cytostatic or surgical therapy of tumors, and thus, development of gentle and specific tumoricidal therapies like targeted photodynamic approaches may help spare the normal tissue of oncology patients (134). Although in some other oncological strategies there has been a considerable effort made toward inhibition and/or destruction of blood vessels to devitalize tumor tissues (135), the opposite effort is usually exercised in tissue engineering and wound healing research (136,137) to keep regenerating or engineered tissues alive and functional. Three major areas of vessel engineering can be distinguished: i) reconstruction of large vessels using transplants and prostheses, ii) creation or induction of vessels in bioengineered constructs (i.e., imitation of embryonic vasculogenesis), and iii) enhancement of vessel invasion into the engineered material from the neighboring tissues (angiogenesis).…”

Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques

“…More importantly, these beneficial effects seemed to be mediated through paracrine effects [44]. MSCs can attract macrophages, VSMCs and other types of cells to the wound site to release a variety of angiogenic factors involved in tissue repair [45, 46]. MSCs stimulate the release of paracrine factors, thus playing a role in the paracrine mechanism, thereby inducing the function of endogenous tissue cells [47, 48].…”