Transcriptional profile of in vitro expanded human epidermal progenitor cells for the treatment of non-healing wounds

Langa, Paulina; Wardowska, Anna; Zieliński, Jacek; Podolak-Popinigis, Justyna; Sass, Piotr; Sosnowski, Paweł; Kondej, Karolina; Renkielska, Alicja; Sachadyn, Paweł; Trzonkowski, Piotr; Pikuła, Michał

doi:10.1016/j.jdermsci.2017.12.003

Cited by 12 publications

(9 citation statements)

References 42 publications

(46 reference statements)

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“…In recent years, much attention has been paid to the use of cell therapies in the treatment of wounds. For example, epidermal stem cells were first used in wound treatment in 1981 and are now applied to promote healing of burns and chronic wounds 17,18 . Autologous genetically modified cultured epidermal stem cells were also successfully used in a clinical trial for junctional epidermolysis bullosa 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Deptuła

Brzezicka

Skoniecka

et al. 2021

Medicinal Research Reviews

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Wound healing complications affect thousands of people each year, thus constituting a profound economic and medical burden. Chronic wounds are a highly complex problem that usually affects elderly patients as well as patients with comorbidities such as diabetes, cancer (surgery, radiotherapy/chemotherapy) or autoimmune diseases. Currently available methods of their treatment are not fully effective, so new solutions are constantly being sought. Cell‐based therapies seem to have great potential for use in stimulating wound healing. In recent years, much effort has been focused on characterizing of adipose‐derived mesenchymal stromal cells (AD‐MSCs) and evaluating their clinical use in regenerative medicine and other medical fields. These cells are easily obtained in large amounts from adipose tissue and show a high proregenerative potential, mainly through paracrine activities. In this review, the process of healing acute and nonhealing (chronic) wounds is detailed, with a special attention paid to the wounds of patients with diabetes and cancer. In addition, the methods and technical aspects of AD‐MSCs isolation, culture and transplantation in chronic wounds are described, and the characteristics, genetic stability and role of AD‐MSCs in wound healing are also summarized. The biological properties of AD‐MSCs isolated from subcutaneous and visceral adipose tissue are compared. Additionally, methods to increase their therapeutic potential as well as factors that may affect their biological functions are summarized. Finally, their therapeutic potential in the treatment of diabetic and oncological wounds is also discussed.

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Section: Introductionmentioning

confidence: 99%

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Deptuła

Brzezicka

Skoniecka

et al. 2021

Medicinal Research Reviews

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“…Sabapathy et al published their findings that Wharton's Jelly-derived MSCs cultured in serum-free media increased regeneration of a skin injury in mice [52]. Serum-free expanded autologous epidermal cells were shown to establish closure of a chronic wound in a patient [53]. Thus, the availability of data using serum-free cells in (pre)-clinical wound healing studies is still scarce.…”

Section: Discussionmentioning

confidence: 99%

Multipotent adult progenitor cells grown under xenobiotic-free conditions support vascularization during wound healing

Vaes¹,

Houtven²,

Caluwé

et al. 2020

Stem Cell Res Ther

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Background Cell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing. While translation of this approach to clinical practice ideally requires the availability of clinical grade xenobiotic-free cell preparations, studies proving the pre-clinical efficacy of the latter are mostly lacking. Here, the potential of xenobiotic-free human multipotent adult progenitor cell (XF-hMAPC®) preparations to promote vascularization was evaluated. Methods The potential of XF-hMAPC cells to support blood vessel formation was first scored in an in vivo Matrigel assay in mice. Next, a dose-response study was performed with XF-hMAPC cells in which they were tested for their ability to support vascularization and (epi) dermal healing in a physiologically relevant splinted wound mouse model. Results XF-hMAPC cells supported blood vessel formation in Matrigel by promoting the formation of mature (smooth muscle cell-coated) vessels. Furthermore, XF-hMAPC cells dose-dependently improved wound vascularization associated with increasing wound closure and re-epithelialization, granulation tissue formation, and dermal collagen organization. Conclusions Here, we demonstrated that the administration of clinical-grade XF-hMAPC cells in mice represents an effective approach for improving wound vascularization and healing that is readily applicable for translation in humans.

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“…Confirmation of “stemness” of these cells was performed by flow cytometry and analysis of differentiation potential into adipocytes, osteocytes, and chondrocytes ( Figure S14 ), as previously described by Mieczkowska et al [ 56 ], and the protocol is summarized in the Supplementary file. Primary epidermal cells were isolated with the protocol described earlier by Langa et al [ 58 ] and fibroblasts by culture of explants. To allow cells to grow out from the tissue samples, human dermis was placed in six-well plates containing Dulbecco’s modified Eagle’s medium high glucose (4500 mg/L) medium supplemented with 10% of fetal bovine serum (FBS, Sigma-Aldrich, St. Louis, MO, USA), 100 U/mL of penicillin, and 100 μg/mL streptomycin (Sigma-Aldrich, MO, USA), then placed under standard conditions in a humidified atmosphere with 5% CO 2 at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Imunofan—RDKVYR Peptide—Stimulates Skin Cell Proliferation and Promotes Tissue Repair

et al. 2020

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Regeneration and wound healing are vital to tissue homeostasis and organism survival. One of the biggest challenges of today’s science and medicine is finding methods and factors to stimulate these processes in the human body. Effective solutions to promote regenerative responses will accelerate advances in tissue engineering, regenerative medicine, transplantology, and a number of other clinical specialties. In this study, we assessed the potential efficacy of a synthetic hexapeptide, RDKVYR, for the stimulation of tissue repair and wound healing. The hexapeptide is marketed under the name “Imunofan” (IM) as an immunostimulant. IM displayed stability in aqueous solutions, while in plasma it was rapidly bound by albumins. Structural analyses demonstrated the conformational flexibility of the peptide. Tests in human fibroblast and keratinocyte cell lines showed that IM exerted a statistically significant (p < 0.05) pro-proliferative activity (30–40% and 20–50% increase in proliferation of fibroblast and keratinocytes, respectively), revealed no cytotoxicity over a vast range of concentrations (p < 0.05), and had no allergic properties. IM was found to induce significant transcriptional responses, such as enhanced activity of genes involved in active DNA demethylation (p < 0.05) in fibroblasts and activation of genes involved in immune responses, migration, and chemotaxis in adipose-derived stem cells derived from surgery donors. Experiments in a model of ear pinna injury in mice indicated that IM moderately promoted tissue repair (8% in BALB/c and 36% in C57BL/6 in comparison to control).

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Transcriptional profile of in vitro expanded human epidermal progenitor cells for the treatment of non-healing wounds

Abstract: The cells cultured in serum-free media display epidermal stem cells features and a potential to stimulate wound healing. This promising procedure of isolation, culture and application warrants further clinical trials in the treatment of chronic wounds.

Cited by 12 publications

References 42 publications

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Adipose‐derived stromal cells for nonhealing wounds: Emerging opportunities and challenges

Multipotent adult progenitor cells grown under xenobiotic-free conditions support vascularization during wound healing

Imunofan—RDKVYR Peptide—Stimulates Skin Cell Proliferation and Promotes Tissue Repair

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