INVESTIGATIVE REPORT
593 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV
Dermal CD271 + Cells are Closely Associated with Regeneration of the Dermis in the Wound Healing Process
Yohei IWATA 1, Yuichi HASEBE 2, 3, Seiji HASEGAWA 1 – 3, Satoru NAKATA 2, Akiko YAGAMI 1, Kayoko MATSUNAGA 1, Kazumitsu SUGIURA 1 and Hirohiko AKAMATSU 4
1
Department of Dermatology, Fujita Health University School of Medicine, 2 Research Laboratories, Nippon Menard Cosmetic Co., Ltd, 3 MENARD Collaborative Research Chair, Nagoya University Graduate School of Medicine, 4 Department of Applied Cell and Regenerative Medicine, Fujita Health University School of Medical, Aichi, Japan
Stem cells have recently been shown to play important roles in wound healing. The aim of this study was to investigate the role of dermal CD271 + cells in wound healing. Full-thickness wounds were produced on the backs of 5-year-old and 24-week-old mice, and timecourse of wound closure, CD271 + cell counts, and gene expression levels were compared. Delayed wound healing was observed in 24-week-old mice. The peak of CD271 + cell increase was delayed in 24-week-old mice, and gene expression levels of growth factors in wounded tissue were significantly increased in 5-year-old mice. Dermal CD271 + cells purified by fluorescenceactivated cell sorting( FACS) expressed higher growth factors than CD271 – cells, suggesting that CD271 + cells play important roles by producing growth factors. This study also investigated dermal CD271 + cells in patients with chronic skin ulcers. Dermal CD271 + cells in patients were significantly reduced compared with in healthy controls. Thus, dermal CD271 + cells are closely associated with wound healing.
Key words: CD271; p75NTR; stem cell; wound healing; collagen type V.
Accepted Jan 25, 2017; Epub ahead of print Jan 27, 2017 Acta Derm Venereol 2017; 97: 593 – 600.
Corr: Yohei Iwata, Department of Dermatology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. E-mail: iwayou @ fujita-hu. ac. jp
Healing of cutaneous wounds is a complex biological event involving interplay of a large number of resident and infiltrating inflammation cells. Although new therapeutic methods have been developed, the available treatments for chronic skin ulcers remain unsatisfactory, and more-effective treatment strategies are needed. Recently, it has been reported that clinical application of stem cells can improve wound healing in the skin( 1, 2). In addition, adipose tissues serve as a source of adipokines and cytokines, with both local and systemic effects on health and disease( 3), suggesting that stem cells could be a new therapeutic option for chronic skin ulcers. Stem cells are categorized into 3 types: embryonic, adult, and induced pluripotent stem cells. The most common types of adult stem cells are haematopoietic stem cells, bone marrow-derived mesenchymal stem cells( MSCs) and adipose-derived stem cells( ASCs). Since it is necessary to easily, safely, and efficiently collect a sufficient number of cells for clinical applications, ASCs are more suitable for clinical applications compared with bone marrow-derived MSCs. Although many stem cell-associated markers for ASCs have been reported, including Lin, Integrin beta-1, CD34, Sca-1, and CD24( 4), a definite marker for ASCs remains unclear. Recently, we confirmed that p75 neurotrophin receptor( p75NTR; CD271)-positive cells in subcutaneous adipose tissues possessed multipotency( 5). In addition, a previous study demonstrated that CD271 is a common stem cell marker for the epidermis and dermis, and that CD271 + cells are characterized by excellent proliferation and multipotency( 6). Since the CD271 + subset consists of heterogeneous cell populations and contains a large population of stem cells, CD271 + cells are a“ CD271 + stem cell-enriched population”.
Recently, we clarified that epidermal CD271 + stem cells play an important role in the wound healing process in mice( 7). Furthermore, we demonstrated that epidermal CD271 + cells were decreased in chronic ulcers in humans( 7). In addition, we have previously confirmed that dermal CD271 + cells have a high proliferation potential and are able to differentiate into adipocytes, osteoblasts and chondrocytes( 6). Therefore, we hypothesize that dermal CD271 + cells are increased and play important roles in wound healing by producing various growth factors or cytokines. The aim of this study was therefore to investigate the dynamic movement timecourse of dermal CD271 + cells, accumulation of several kind of collagen, and gene expression levels of various cytokines and growth factors during the wound healing process in mice. A further aim was to investigate dermal CD271 + cell numbers in patients with chronic skin ulcers. The results indicate that dermal CD271 + cells are closely associated with regeneration of the dermis in wound healing by producing various growth factors. Furthermore, dermal CD271 + cells in patients with chronic skin ulcers were significantly reduced compared with healthy controls. These results suggest that dermal CD271 + cells are closely associated with regeneration of the dermis in wound healing.
METHODS Mice
HR-1 mice were purchased from Hoshino Laboratory Animals( Ibaraki, Japan). All mice were healthy and fertile, and did not
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2624 Acta Derm Venereol 2017; 97: 593 – 600