**9. Bone marrow concentrates in chronic wounds**

Cell-based therapies are an attractive approach for the treatment of recalcitrant chronic wounds. BM-MSCs have been studied as a therapeutic strategy in chronic hard-to-heal wounds [135]. The orchestrated process of wound healing entails cellular and hormonal physiological processes in inflammation, proliferation, collagen matrix formation, and epithelialization which are regulated by various platelet-derived growth factors, such as TGF-b, VEGF, PDGF, granulocytemacrophage colony-stimulating factor, the interleukin family, EGF, FGF, and TNF-a [44, 105]. In chronic, poor-healing wounds, the activity and effectivity of growth factors and cytokines are often reduced due to a chronically inflamed wound.

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needed [45].

**11. Conclusions**

*The Rationale of Autologously Prepared Bone Marrow Aspirate Concentrate for use…*

Under these conditions the neo-angiogenetic wound healing potential is reduced, resulting in poor or no full wound epithelialization. The rationale for using BMC in these patients is the potential to modulate the immune response and secreting paracrine factors which promote (neo) angiogenesis, thereby providing biological ingredients for wound tissue repair that can jumpstart full wound closure [76, 136]. Optimal wound bed preparation is of the essence in wound healing strategies and encompasses tissue debridement with proper management of the bacterial load. Based on BM-MSC characteristics and their biological activity, MSCs are capable of interacting with resident wound cells to transform resident cells to functional matrix building cells, as described by Balaji et al. [137]. This finding might be of particular importance for dermal rebuilding processes, to stimulate (transplanted)

Patients with significant, below the knee, vascular diseases and who are, first of all, not eligible for revascularization surgery or endovascular treatments due to several comorbidities or have high operative risk and had multiple failures of revascularization or high rate of re-stenosis, might be suitable candidates for biological cell-based therapy with BM-MSCs. Patients diagnosed with critical limb ischemia (CLI) might also suffer from chronic non-healing wounds, and the estimated amputation and mortality rates are high [138]. The application of regenerative medicine therapies, in particular the use of BM-MSCs protocols, has merged as a treatment option in patients with CLI. In these patients, the justification to use BMC is to promote the regeneration of impaired endothelium and stimulate neoangiogenesis in ischemic areas [139]. Several varieties of BM-MSC therapies have been studied in CLI patients, ranging from BM-derived mononuclear cells, CD34+ BM cells, to mesenchymal stromal cells. The outcomes of cell-based trials have been encouraging and demonstrated a significant decrease in the rate of amputation [140]. It can be concluded that BM-MSC applications have the potential to modify the natural history of intractable CLI, while high-quality randomized trials are

Regenerative medicine technologies offer solutions to a number of compelling clinical problems that have not been able to adequately result in a solution through the use of drugs, surgery, or permanent replacement devices. Reviewing the last decades regarding autologous biological therapies, BM-MSCs have gained great interest. The purpose of this chapter was to review specific characteristics of bone marrow tissue and its cellular content, in particular the mesenchymal stem cells. Considerations when performing aspiration techniques and bone marrow concentrate preparations were presented, including explicit roles of hematopoietic and mesenchymal stem cells and other cytokines. Among autologous tissue-based cellular therapies, bone marrow mesenchymal cell therapies have been the most frequently employed and reported on, despite the fact that effects of coadjuvants, dosing, repetitive procedures, etc. are not yet established. Cultured MSC therapeutic interventions require strict procedures and biological license agreements, making them less attractive for same-day regenerative therapies. Using at POC BM-MSC concentrates overcomes these lengthy regulatory processes without the need for mandates. Clinical translation of BM-MSC-based therapies remains a work

*DOI: http://dx.doi.org/10.5772/intechopen.91310*

keratinocyte-mediated wound epithelialization.

**10. Bone marrow concentrates in critical limb ischemia**

*The Rationale of Autologously Prepared Bone Marrow Aspirate Concentrate for use… DOI: http://dx.doi.org/10.5772/intechopen.91310*

Under these conditions the neo-angiogenetic wound healing potential is reduced, resulting in poor or no full wound epithelialization. The rationale for using BMC in these patients is the potential to modulate the immune response and secreting paracrine factors which promote (neo) angiogenesis, thereby providing biological ingredients for wound tissue repair that can jumpstart full wound closure [76, 136]. Optimal wound bed preparation is of the essence in wound healing strategies and encompasses tissue debridement with proper management of the bacterial load. Based on BM-MSC characteristics and their biological activity, MSCs are capable of interacting with resident wound cells to transform resident cells to functional matrix building cells, as described by Balaji et al. [137]. This finding might be of particular importance for dermal rebuilding processes, to stimulate (transplanted) keratinocyte-mediated wound epithelialization.
