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Superiority of Adipose-derived CD34 + Cells over Adipose-derived Stem Cells in Promoting Ischemic Tissue Survival

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Abstract

Background

Tissue ischemia usually leads to necrosis and is a threatening condition associated with reconstructive surgery. Promoting the survival of ischemic tissue is critical for improving clinical outcomes. Although various solutions based on stem cells have been reported, there are still limitations to clinical translation. The aim of this study was to develop an effective method to promote the survival of ischemic tissue.

Methods

Adipose-derived CD34 + and CD34- cells were obtained by magnetic bead sorting from the stromal vascular faction (SVF). Adipose-derived stem cells (ADSCs) were collected by subculture. The angiogenic capacities of CD34 + cells, CD34- cells and ADSCs were evaluated in vitro by comparing mRNA and protein expression. Random axial flaps in nude mice were used to evaluate the efficacy of these cells in protecting tissue from necrosis. The effect of these cells in preventing inflammation was also evaluated.

Results

Our data suggest that CD34 + cells expressed higher levels of angiogenetic factors and lower levels of inflammatory factors than the other cell types. More vessel branches were formed when human umbilical vein endothelial cells (HUVECs) were treated with conditioned medium from CD34 + cells than conditioned medium from the other cell types. Compared to ADSCs, CD34 + cells showed significantly higher efficacy in promoting tissue survival. More CD31 + cells and higher levels of angiogenic factors were observed in tissues from the CD34 + group than in those from the other groups. Lower levels of the proinflammatory factors TNF-α and IL-1b and higher levels of anti-inflammatory factors were found in the CD34 + group than in the other groups.

Conclusion

Adipose-derived CD34 + cells showed better efficacy in improving ischemic tissue survival than ADSCs by reducing tissue inflammation and promoting angiogenesis. CD34 + cells can be obtained easily and may be suitable for clinical applications.

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Abbreviations

ADSC:

adipose-derived stem cell

BSA:

bovine serum albumin

EPCs:

endothelial progenitor cells

HSCs:

hematopoietic stem cells

HUVECs:

human umbilical vein endothelial cells

MSCs:

mesenchymal stem cells

PVDF:

polyvinylidene difluoride

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Acknowledgements

The authors gratefully acknowledge the technology support from the Core Facility of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine. We thank American Journal Experts (AJE) for editing the English language of the manuscript. Figures were created using Microsoft Powerpoint and Biorender.

Funding

This study was supported by the National Natural Science Foundation of China (81971848; 81620108019); Clinical Research Plan of SHDC (SHDC2020CR1019B; SHC2020CR402); Shanghai Municipal Key Clinical Specialty (shslczdzk00901); and Innovative Research Team of High-level Local University in Shanghai (SSMU-ZDCX20180700).

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Author notes

  1. YJ Liu, TY Zhang and PC Tan contributed equally to this work and are considered to be co-first authors.

Authors and Affiliations

  1. Department of Plastic & Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizhaoju Road, Shanghai, People’s Republic of China, 200011

    Yan-Jun Liu, Tian-Yu Zhang, Poh-Ching Tan, Pei-Qi Zhang, Yun Xie, Qing-Feng Li & Shuang-Bai Zhou

  2. College of Life Sciences, Shanghai Normal University, Shanghai, China

    Tian-Yu Zhang

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  1. Yan-Jun Liu
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Contributions

YJL, SBZ and QFL initiated and designed the study and protocol. SBZ and YX recruited all patients. YJL, TYZ and PCT participated in the data collection and data analysis. PCT and PQZ contributed to the data interpretation. TYZ and PCT wrote the first draft of the manuscript, and QFL and SBZ critiqued and modified the manuscript. All authors reviewed and approved the work.

Corresponding author

Correspondence to Shuang-Bai Zhou.

Ethics declarations

Ethics Approval and Consent to Participate

The donors of abdominal subcutaneous adipose tissues all provided informed consent. This study was approved by the Ethics Committee of Shanghai Ninth People's Hospital and complied with the principles of the Declaration of Helsinki. Consent to participate is not applicable.

Consent for Publication

Not applicable.

Graphical Illustrations

Graphical illustrations were made with Biorender.com.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing Interests

The authors declare that they have no competing interests.

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Liu, YJ., Zhang, TY., Tan, PC. et al. Superiority of Adipose-derived CD34 + Cells over Adipose-derived Stem Cells in Promoting Ischemic Tissue Survival. Stem Cell Rev and Rep 18, 660–671 (2022). https://doi.org/10.1007/s12015-021-10276-x

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