Human bone marrow‐derived cells: An attractive source to populate dermal substitutes

Abstract

We have previously shown the importance of dermal fibroblasts within skin substitutes for promoting the emergence of a functional neodermis after grafting in humans. However, the use of fibroblasts from sources other than the dermis needs to be evaluated for patients with extensive skin loss. Here we examined the capacity of human bone marrow-derived cells (BMDCs), selected for their ability to adhere to plastic culture dishes, to behave like human dermal fibroblasts when incorporated within a 3D in vitro reconstructed tissue that promotes dermal fibroblast differentiation. Like dermal fibroblasts, BMDCs contracted a collagen matrix and were growth regulated by the matrix environment. They had the same shape and their nuclei had the same form factor as dermal fibroblasts. In addition, both cell types expressed desmin and vimentin but not alpha-smooth muscle actin. BMDCs deposited collagen types I and III, and fibrillin-1 with similar efficiency to dermal fibroblasts. In addition, BMDCs have the potential to regulate this deposition, as they produced metalloproteinases (MMP1, MMP2, and MMP9) and metalloproteinase inhibitors (TIMP1) very similarly to dermal fibroblasts. BMDCs can thus be induced to express functions resembling those of dermal fibroblasts, including those involved in the wound healing process.

Emerging therapy for improving wound repair of severe radiation burns using local bone marrow-derived stem cell administrations

“…14 More recently, Fioretti et al 15 demonstrated that human bone marrow-derived cells exhibited biological functions very similar to dermal fibroblasts including those involved in the wound-healing process. While the mechanism of MSC in skin repair remains speculative, we believe that they play a key role through their trophic activity.…”

“…The main features of radiation skin burns, if compared with thermal burns, are firstly, a very marked dose dependence of the clinical pattern (dry epidermitis (12)(13)(14)(15), moist desquamation (15)(16)(17)(18)(19)(20), and necrosis ( > 25-30 Gy), secondly, the association with a paroxysmal and chronic pain resistant to opiates, and thirdly, the occurrence of uncontrolled successive inflammatory waves during several weeks, months, or years. In all cases, the healing is long, frail, and uncertain.…”

Challenges in the Treatment of Chronic Wounds

“…30,282,283 Although much interest has focused on orthopedic and critical limb ischemia applications, BMSCs are increasingly being studied for use in enhancing chronic wound and cutaneous repair. 118,[284][285][286][287][288][289][290][291] Several articles and clinical studies have specifically focused on DFU management. [292][293][294] One of the earlier studies by Yamaguchi et al took a novel approach by decorticating exposed bone at the base of the ulcer to locally release bone marrow cells directly into the wound.…”

The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture

“…However, incorporation of fibroblasts in the dermal substitutes facilitate the formation of stratified epidermis in vitro [20,21], which suggests the crucial role of mesenchymal-interactions in epidermal development. Later it was found that dermal fibroblasts could be substituted with MSCs or preadipocytes to achieve a superior epidermal stratification [14,22,23]. In further OC experiments pure MSCs were cultured on top of fibroblast-embedded dermal substitutes showing the potential of MSCs to transdifferentiate into KERs lineage under specific conditions.…”

“…Recently the influence of BM-MSCs in the dermal equivalent was investigated and they were found to demonstrate functions resembling those of dermal fibroblasts during wound healing process [14]. However, an investigation of BM-MSCs in epidermal development in vitro has not been done so far.…”