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Review
. 2015 Oct;4(10):1187-98.
doi: 10.5966/sctm.2015-0084. Epub 2015 Aug 7.

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

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Free PMC article
Review

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

Natalia Vapniarsky et al. Stem Cells Transl Med. .
Free PMC article

Abstract

The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering.

Significance: Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use.

Keywords: Adult dermis mesenchymal stem cells; Autologous tissue engineering; Bulge stem cells; Dermal papilla stem cells; Dermal sheath; Multilineage differentiation; Pericytes; Sebaceous gland stromal stem cells; Stemness.

Figures

Figure 1.
Figure 1.
The developmental steps from the blastocyst stage to the development of somites, lateral line mesenchyme, and neural crest. (A): Day 8 of development. Blastocyst implantation into uterine mucosa is shown. (B): Days 8–14 of development. Amniotic cavity enlarges, ectoderm becomes apparent, and endoderm completely covers the cavity of primitive gut (yolk sac cavity). (C): Days 15–19 of development. Primitive streak appears, indicating the beginning of gastrulation, in which the third layer of the embryo forms (the mesoderm). Formation of mesoderm occurs through a process of cellular migration of ectodermal cells downward (curved arrows) at the level of the primitive streak. (D): Days 19–21 of development. Ectoderm folds in to form a neural groove. Before complete closure of the neural groove, a group of cells detach to form a neural crest. Mesodermal plate divides into notochord, paraxial mesoderm (future somites), intermediate mesoderm (future nephros), and lateral plate mesoderm. (E): Day 48 of development. The neural groove is now closed (neural tube); the mesoderm further expands and develops to give rise to muscles, bones, fat, and dermis. (F): Mature skin. The adult skin components are represented in colors matching their embryonic origin as shown in previous panels. Despite uniform histological appearance, the dermis of the head is of neural crest origin, the dermis of the dorsal skin is of paraxial mesoderm origin, and the dermis of the body wall and extremities is of lateral plate origin. The epidermis throughout the body is of ectodermal origin. The melanocytes and the stem cells of the bulge portion of the hair follicle are of neural crest origin.
Figure 2.
Figure 2.
Dermal stem cell niches and the potential of stem cells residing in them to differentiate along different lineages. Schematic of skin section containing a hair follicle. The chart lists major tissue lineages that were derived from dermis stem cells according to niche (HFP [3, 5, 28], DS [28], B [32], P [2, 35], and SGSC [37]). Abbreviations: B, hair follicle bulge; DS, dermal sheath; HFP, hair follicle papilla; P, pericytes; SGSC, sebaceous gland stromal stem cells.
Figure 3.
Figure 3.
Histochemical stains are not specific enough for demonstration of lineage differentiation. (A–C): Examples of native bone, cartilage, and adipose tissues stained with von Kossa, Alcian blue, and Oil Red O, respectively. (A): A nondecalcified equine trabecular bone embedded in Technovit resin, stained with von Kossa. (B): Tracheal bovine cartilage stained with Alcian blue (pH 1) and counterstained with nuclear fast red. (C): A cryosection of human adipose tissue stained with Oil Red O. (D): Avian lung affected by metastatic mineralization, stained with von Kossa and counterstained with nuclear fast red. (E): Normal canine colon stained with Alcian blue (pH 1) and counterstained with nuclear fast red, highlighting the goblet cells filled with mucopolysaccharides. (F): A cryosection of bovine liver affected by severe lipidosis, stained with Oil Red O. (G): Canine kidney affected by severe tubular mineralization, stained with von Kossa. (H): Canine oral neoplasm with myxomatous metaplasia, stained with Alcian blue (pH 1) and counterstained with nuclear fast red. (I): A cryosection of atherosclerotic plaque from a blood vessel of a primate, stained with Oil Red O. Scale bars = 200 μm.

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