title: Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration: A Randomized Phase I/II Clinical Trial.
abstract: BACKGROUND
  Mechanical stretch, in term of skin expansion, can induce effective but limited in vivo skin regeneration for complex skin defect reconstruction. We propose a strategy to obtain regenerated skin by combining autologous stem cell transplantation with mechanical stretch.
  
  
  METHODS
  This randomized, blinded placebo-controlled trial enrolled 38 adult patients undergoing skin expansion presenting with signs of exhausted regenerative capacity. Patients randomly received autologous bone marrow mononuclear cell (MNC) or placebo injections intradermally. Follow-up examinations were at 4, 8weeks and 2years. The primary endpoint was the volume achieved in relation to the designed size of the expander (expansion index, EI). Secondary endpoints were surface area, thickness and texture of expanded skin. This trial is registered with ClinicalTrial.gov, NCT01209611.
  
  
  RESULTS
  The MNC group had a significantly higher EI at 4weeks (mean difference 0.59 [95% CI, 0.03-1.16]; p=0.039) and 8weeks (1.05 [95% CI, 0.45-1.66]; p=0.001) versus controls. At 8weeks, the MNC group had significantly thicker skin (epidermis: p<0.001, dermis: p<0.001) and higher subjective scores for skin quality/texture (24.8 [95% CI, 17.6-32.1]; p<0.001). The MNC group had more skin surface area (70.34cm2[95% CI, 39.75-100.92]; p<0.001). Patients in the MNC group gained up to the quadrupled surface area of expanded skin compared to pre-expansion at the end of expansion. No severe adverse events occurred.
  
  
  CONCLUSIONS
  Intradermal transplantation of autologous stem cells represents a safe and effective strategy to promote in vivo mechanical stretch induced skin regeneration, which can provide complex skin defect reconstruction with plentiful of tissue.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Shuang-Bai
authors.initials: SB
authors.lastname: Zhou
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Guo-You
authors.initials: GY
authors.lastname: Zhang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zan
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Yao-Kai
authors.initials: YK
authors.lastname: Gan
authors.affiliation: Division of Plastic and Reconstructive Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Yao
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Cheng-An
authors.initials: CA
authors.lastname: Chiang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Plastic and Reconstructive Surgery, University of California Davis Medical Center, Sacramento, CA, United States.
authors.forename: Lee Q
authors.initials: LQ
authors.lastname: Pu
authors.affiliation: Division of Plastic and Reconstructive Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States.
authors.forename: William P
authors.initials: WP
authors.lastname: Magee
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Electronic address: dr.liqingfeng@shsmu.edu.cn.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Li
mesh_terms: D000328:Adult; D015415:Biomarkers; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D055595:Mechanical Phenomena; D008875:Middle Aged; D012038:Regeneration; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012879:Skin Physiological Phenomena; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Autologous stem cell; Bone mononuclear cells; Mechanical stretch; Skin expansion; Skin regeneration