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