Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration

A Randomized Phase I/II Clinical Trial

Shuang Bai Zhou, Guo You Zhang, Yun Xie, Tao Zan, Yao Kai Gan, Caroline A. Yao, Cheng An Chiang, Jing Wang, Kai Liu, Hua Li, Jia Zhou, Mei Yang, Bin Gu, Feng Xie, Lee Li-Qun Pu, William P. Magee, Qing Feng Li

Research output: Contribution to journalArticle

3 Citations (Scopus)

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, 8 weeks and 2 years. 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. Findings The MNC group had a significantly higher EI at 4 weeks (mean difference 0.59 [95% CI, 0.03–1.16]; p = 0.039) and 8 weeks (1.05 [95% CI, 0.45–1.66]; p = 0.001) versus controls. At 8 weeks, 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 (70.34 cm2 [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. Interpretation 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.

Original languageEnglish (US)
Pages (from-to)356-364
Number of pages9
JournalEBioMedicine
Volume13
DOIs
StatePublished - Nov 1 2016

Fingerprint

Phase II Clinical Trials
Clinical Trials, Phase I
Stem Cell Transplantation
Stem cells
Regeneration
Skin
Randomized Controlled Trials
Textures
Placebos
Defects
Dermis
Epidermis
Bone Marrow Cells
Bone

Keywords

  • Autologous stem cell
  • Bone mononuclear cells
  • Mechanical stretch
  • Skin expansion
  • Skin regeneration

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration : A Randomized Phase I/II Clinical Trial. / Zhou, Shuang Bai; Zhang, Guo You; Xie, Yun; Zan, Tao; Gan, Yao Kai; Yao, Caroline A.; Chiang, Cheng An; Wang, Jing; Liu, Kai; Li, Hua; Zhou, Jia; Yang, Mei; Gu, Bin; Xie, Feng; Pu, Lee Li-Qun; Magee, William P.; Li, Qing Feng.

In: EBioMedicine, Vol. 13, 01.11.2016, p. 356-364.

Research output: Contribution to journalArticle

Zhou, SB, Zhang, GY, Xie, Y, Zan, T, Gan, YK, Yao, CA, Chiang, CA, Wang, J, Liu, K, Li, H, Zhou, J, Yang, M, Gu, B, Xie, F, Pu, LL-Q, Magee, WP & Li, QF 2016, 'Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration: A Randomized Phase I/II Clinical Trial', EBioMedicine, vol. 13, pp. 356-364. https://doi.org/10.1016/j.ebiom.2016.09.031
Zhou, Shuang Bai ; Zhang, Guo You ; Xie, Yun ; Zan, Tao ; Gan, Yao Kai ; Yao, Caroline A. ; Chiang, Cheng An ; Wang, Jing ; Liu, Kai ; Li, Hua ; Zhou, Jia ; Yang, Mei ; Gu, Bin ; Xie, Feng ; Pu, Lee Li-Qun ; Magee, William P. ; Li, Qing Feng. / Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration : A Randomized Phase I/II Clinical Trial. In: EBioMedicine. 2016 ; Vol. 13. pp. 356-364.
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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, 8 weeks and 2 years. 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. Findings The MNC group had a significantly higher EI at 4 weeks (mean difference 0.59 [95{\%} CI, 0.03–1.16]; p = 0.039) and 8 weeks (1.05 [95{\%} CI, 0.45–1.66]; p = 0.001) versus controls. At 8 weeks, 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 (70.34 cm2 [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. Interpretation 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.",
keywords = "Autologous stem cell, Bone mononuclear cells, Mechanical stretch, Skin expansion, Skin regeneration",
author = "Zhou, {Shuang Bai} and Zhang, {Guo You} and Yun Xie and Tao Zan and Gan, {Yao Kai} and Yao, {Caroline A.} and Chiang, {Cheng An} and Jing Wang and Kai Liu and Hua Li and Jia Zhou and Mei Yang and Bin Gu and Feng Xie and Pu, {Lee Li-Qun} and Magee, {William P.} and Li, {Qing Feng}",
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T2 - A Randomized Phase I/II Clinical Trial

AU - Zhou, Shuang Bai

AU - Zhang, Guo You

AU - Xie, Yun

AU - Zan, Tao

AU - Gan, Yao Kai

AU - Yao, Caroline A.

AU - Chiang, Cheng An

AU - Wang, Jing

AU - Liu, Kai

AU - Li, Hua

AU - Zhou, Jia

AU - Yang, Mei

AU - Gu, Bin

AU - Xie, Feng

AU - Pu, Lee Li-Qun

AU - Magee, William P.

AU - Li, Qing Feng

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N2 - 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, 8 weeks and 2 years. 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. Findings The MNC group had a significantly higher EI at 4 weeks (mean difference 0.59 [95% CI, 0.03–1.16]; p = 0.039) and 8 weeks (1.05 [95% CI, 0.45–1.66]; p = 0.001) versus controls. At 8 weeks, 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 (70.34 cm2 [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. Interpretation 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.

AB - 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, 8 weeks and 2 years. 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. Findings The MNC group had a significantly higher EI at 4 weeks (mean difference 0.59 [95% CI, 0.03–1.16]; p = 0.039) and 8 weeks (1.05 [95% CI, 0.45–1.66]; p = 0.001) versus controls. At 8 weeks, 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 (70.34 cm2 [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. Interpretation 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.

KW - Autologous stem cell

KW - Bone mononuclear cells

KW - Mechanical stretch

KW - Skin expansion

KW - Skin regeneration

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