“…A supply of healthy cells capable of contributing to tissue repair and regeneration without risk of host rejection or malignant transformation is vital to achieving this goal. In this regard, bone marrow transplantation and skin and bone grafts have proven clinical utility (1)(2)(3)(4). However, for the majority of tissues that require regeneration, harvesting and expanding stem and progenitor cells is a challenge, and tissue grafting is not an option due to siteand tissue-specific limitations.…”
Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to a receptive growth factor might result in the expansion of a plastic and proliferative population of cells. To this end, we treated lineage-committed cells with AZA and screened a number of different growth factors with known activity in mesenchyme-derived tissues. Here, we report that transient treatment with AZA in combination with platelet-derived growth factor–AB converts primary somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells possess a distinct transcriptome, are immunosuppressive, and demonstrate long-term self-renewal, serial clonogenicity, and multigerm layer differentiation potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner and, unlike embryonic or pluripotent stem cells, do not form teratomas. Taken together, this vector-free method of generating iMS cells from primary terminally differentiated cells has significant scope for application in tissue regeneration.
“…A supply of healthy cells capable of contributing to tissue repair and regeneration without risk of host rejection or malignant transformation is vital to achieving this goal. In this regard, bone marrow transplantation and skin and bone grafts have proven clinical utility (1)(2)(3)(4). However, for the majority of tissues that require regeneration, harvesting and expanding stem and progenitor cells is a challenge, and tissue grafting is not an option due to siteand tissue-specific limitations.…”
Current approaches in tissue engineering are geared toward generating tissue-specific stem cells. Given the complexity and heterogeneity of tissues, this approach has its limitations. An alternate approach is to induce terminally differentiated cells to dedifferentiate into multipotent proliferative cells with the capacity to regenerate all components of a damaged tissue, a phenomenon used by salamanders to regenerate limbs. 5-Azacytidine (AZA) is a nucleoside analog that is used to treat preleukemic and leukemic blood disorders. AZA is also known to induce cell plasticity. We hypothesized that AZA-induced cell plasticity occurs via a transient multipotent cell state and that concomitant exposure to a receptive growth factor might result in the expansion of a plastic and proliferative population of cells. To this end, we treated lineage-committed cells with AZA and screened a number of different growth factors with known activity in mesenchyme-derived tissues. Here, we report that transient treatment with AZA in combination with platelet-derived growth factor–AB converts primary somatic cells into tissue-regenerative multipotent stem (iMS) cells. iMS cells possess a distinct transcriptome, are immunosuppressive, and demonstrate long-term self-renewal, serial clonogenicity, and multigerm layer differentiation potential. Importantly, unlike mesenchymal stem cells, iMS cells contribute directly to in vivo tissue regeneration in a context-dependent manner and, unlike embryonic or pluripotent stem cells, do not form teratomas. Taken together, this vector-free method of generating iMS cells from primary terminally differentiated cells has significant scope for application in tissue regeneration.
“…Records of autogenous skin grafts used to repair mutilations of the nose, ear, and lip appeared in the Sanskrit literature in India centuries ago (Hauben, Baruchin, & Mahler, 1982). Early Indian medicine in the Sanskrit literature referred to the Tilemaker being successful in utilizing free skin grafts including the subcutaneous fat taken from the gluteal region (Hauben et al, 1982).…”
Section: History Of Skin Substitutesmentioning
confidence: 99%
“…Records of autogenous skin grafts used to repair mutilations of the nose, ear, and lip appeared in the Sanskrit literature in India centuries ago (Hauben, Baruchin, & Mahler, 1982). Early Indian medicine in the Sanskrit literature referred to the Tilemaker being successful in utilizing free skin grafts including the subcutaneous fat taken from the gluteal region (Hauben et al, 1982). In the fi fth century AD, Sushrutha, an Indian surgeon, was reported to have used pedicled fl aps and skin grafts to repair mutilations of the ear, nose, and lip as well (Hauben et al, 1982).…”
“…67 The Swiss surgeon Reverdin was the first to use skin allografts to treat wounds: he described an autologous allografting method and in 1869 developed a method known as the "pinch grafting" technique. In 1870, George Lawson proposed a deeper-thickness graft, including epidermis and reticular dermis.…”
mentioning
confidence: 99%
“…69 In 1881, Girdner started to systematically employ autologous skin grafts for burns and wounds. 67,70 He also tried to use allografts: he procured skin Figure 6 Electron transmission microscopy showing preserved the architectural structure of the dermis, integrity of the basal membrane and skin polarization (A). Histocompatibility test with human fibroblasts, colonizing the dermal surface (B).…”
Donor skin and dermal grafts are used in several types of loss of substance for different clinical purposes. As biological physiological medication, donor skin grafts can promote re-epithelization, shorten healing time, alleviate pain and protect dermal and subcutaneous structures such as cartilage, tendons, bones and nerves. Though a great variety of dermal matrices and skin equivalents, both synthetic and semisynthetic, are now available for wound treatment, viable human skin allografts remain an important therapeutic choice for extensive deep burns and hard-to-heal wounds. In such cases, viable skin allografts have significantly better clinical outcomes than unviable human-derived allografts or synthetic medications. The demand for human-derived skin bioproducts continues to be a reason for the existence of skin banks. Skin bank organization is complex and requires continuous updating. Careful donor selection, thorough microbiological and serological donor screening for transmissible diseases and rigorous quality control during tissue preparation are necessary to minimize the risk of transmission of pathogenic agents. Skin banks must also observe standardized reproducible procedures to ensure tissue traceability and biological safety in all phases of processing and to avoid new biological contamination. Constant training and periodic checks are needed to keep skin bank operators attentive and responsible. Finally, skin banks should guarantee collection and storage of highly viable skin. Here, we discuss available tissue storage methods and the different types of skin bioproducts.
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