Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_998_Библиотеки_им_академика_М_И_Перельмана

Still, these efforts often remain unsuccessful and the clinical outcomes suboptimal [7]. Therefore, understanding the unique features of the wound environment is crucial in developing new therapeutic strategies. A variety of new treat­ment modalities such as bioengineered skin sub­stitutes, growth factors, and stem cells are currently being assessed in both preclinical and clinical studies [8, 9]. Among these new thera­peutic options, because of their strong cytokine prole, their immunomodulating properties, and their potential for multilineage differentiation, stem-cell based therapies hold particular promise in the setting of wound repair and tissue regen­eration [10].

Adult stem cells, however, are easier to har­vest and their usage is hardly limited by ethical issues. Beginning of the adult stem cell research can be set in 1963, when Becker etal. [15] rst described the hematopoietic stem cells (HSCs) by reporting the presence of self-replicating cells within the bone marrow of mice. Since then, mul­tiple progenitor cell reservoirs of the adult organ­ism have been discovered and utilized for research and clinical applications. There is evi­dence that adult stem cells may be found in most tissues and organs, predominantly at sites with rapid cell turnover, such as bone marrow, skin, liver, and intestinal mucosa, but also in skeletal muscle tissue, pancreas, heart, and central ner­vous system [16–18]. The most prominent part of these cells turned out to be from mesenchymal origin [19]. Subsequent to their identication as broblasts precursors in bone marrow in the 1950s, mesenchymal stem cells (MSCs) have been isolated from several sites, including adi-

Mesenchymal stem cells may serve as a pow­erful tool to promote tissue regeneration due to two main abilities: secretion of paracrine factors and differentiation [33]. Several studies suggest that the positive effect of stem cell transplanted to the wound site mainly relies on the secretion of pro-regenerative trophic factors, rather than via differentiation and direct replacement of damaged cells [34–37]. The secretome of the

For a long time, the function of the adipose tissue was believed to be limited to the storage of excess energy, and the surplus of tissue was discarded by liposuction or rarely used as a soft-tissue ller. In addition to plastic and reconstructive surgical applications, adipose tissue has become essential to an increasing number of translational efforts involving the understanding of cellular, molecu­lar, and immunological mechanisms. Adipose tis­sue is a heterogeneous entity derived from the mesodermal germ layer, consisting of various cell population [58, 59]. According to the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT), the stromal vascular fraction (SVF) can be dened as a het­erogeneous mesenchymal cell population sepa­rated from the mature adipocytes by processing the adipose tissue [60].

Usually, the SVF is obtained through enzy­matic digestion with collagenase, followed by

The concept of using ASCs as cellular vehi­cles for mediating the therapeutic repair of chronic wounds became very appealing. Adipose tissue, like bone marrow, is a mesodermal deriva­tive and the stroma containing the ASCs can be easily isolated by liposuction under local anes­thesia and with minimal discomfort [56]. A large body of medical literature investigated possible

Therefore, it has been hypothesized that ASCs can initiate and enhance wound healing by two main mechanisms: (1) migration and differentia­tion into skin cells in response to injury and (2) paracrine-mediated activation of broblasts and keratinocytes and down-regulation of the

Several studies have postulated that non­healing wounds are characterized by lack of oxy­gen, chronic systemic inammation, and increased matrix metalloproteinase (MMP) activity, result­ing in degradation of ECM and growth factors [31, 79, 80]. These characteristics of chronic wounds have shown to have a negative impact on the functionality of ASCs. Koenen etal. [81] eval­uated the inuence of acute wound uid (AWF) and chronic wound uid (CWF) on the ASCs. He found out that the CWF signicantly impairs the proliferation and migration of the ASCs, in con­trast with the stimulating effect of the AWF.

84]. Duscher etal. [85] investigated the effect of

In 2006, researchers made another break­through, by discovering that somatic adult cells can be genetically reprogrammed to revert to the previous state of an embryonic stem cells, pre­ceding their initial differentiation status. These so-called iPSCs (induced pluripotent stem cells) were rstly generated by Takahashi and

tial to combine advantages of both stromal cell types, MSCs, and ESCs. Ethical issues that go along with the use of human ESCs can be avoided and autologous iPSCs are highly available and pose a high chance of immunological compatibil­ity. Recent studies have already proven the poten­tial use of iPSCs for cutaneous repair: invitro 3D skin equivalents composed of human iPSC­derived keratinocytes or broblasts have been generated and used for dermal regeneration [106–108]. Moreover, epidermal appendages like the hair follicles could have been generated [109], suggesting that the iPSC-derived skin sub­stitutes are promising for the generation of com­plete cutaneous equivalents. However, further research is needed to determine the ideal meth­ods to completely and reproducibly commit the iPSCs to appropriate cell lineages. The transition of iPScs into the clinic is still hindered by the missing evidence regarding safety and reliability of used reprogramming technologies. Furthermore, issues like the risk for enhanced tumorigenesis and the need for an invitro genetic manipulation and a possible iPSC-mediated immune response need to be addressed before widespread clinical adaption is possible.