2. Academic Validation
  3. Evaluating the pro-survival potential of apoptotic bodies derived from 2D- and 3D- cultured adipose stem cells in ischaemic flaps

Evaluating the pro-survival potential of apoptotic bodies derived from 2D- and 3D- cultured adipose stem cells in ischaemic flaps

  • J Nanobiotechnology. 2024 Jun 14;22(1):333. doi: 10.1186/s12951-024-02533-1.
Gaoxiang Yu # 1 2 3 4,  Jian Ding # 1 2 3,  Ningning Yang # 1 2 3,  Lu Ge 5,  Nuo Chen 5,  Xuzi Zhang 1 2 3,  Qiuchen Wang 5,  Xian Liu 1 2 3,  Xuanlong Zhang 5 2,  Xiaoqiong Jiang 5 2,  Yibo Geng 1 2 3,  Chenxi Zhang 4,  Jiadong Pan 4,  Xiangyang Wang 1 2 3,  Weiyang Gao 1 2 3,  Zhijie Li 1 2 3,  Hongyu Zhang 6,  Wenfei Ni 7 8 9,  Jian Xiao 10,  Kailiang Zhou 11 12 13,  Liangliang Yang 14 15
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, 325027, China.
  • 3 The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325027, China.
  • 4 Department of Hand Surgery, Ningbo Sixth Hospital, Ningbo, 315042, China.
  • 5 School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, 325035, China.
  • 6 School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, 325035, China. st_hyz@126.com.
  • 7 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. niwenfei@126.com.
  • 8 Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, 325027, China. niwenfei@126.com.
  • 9 The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325027, China. niwenfei@126.com.
  • 10 School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, 325035, China. xfxj2000@126.com.
  • 11 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. zhoukailiang@wmu.edu.cn.
  • 12 Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, 325027, China. zhoukailiang@wmu.edu.cn.
  • 13 The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325027, China. zhoukailiang@wmu.edu.cn.
  • 14 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. liangliangyangLLL@126.com.
  • 15 School of Pharmaceutical Sciences, Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, 325035, China. liangliangyangLLL@126.com.
  • # Contributed equally.
PMID: 38877492 DOI: 10.1186/s12951-024-02533-1
Abstract

In the realm of large-area trauma FLAP transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin FLAP survival. Apoptotic bodies (ABs), arising from cell Apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin FLAP survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed Apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of MicroRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin FLAP survival. These effects are attributed to their influence on specific miRNAs.

Keywords

3D cell culture; Adipose-derived mesenchymal stem cells; Apoptotic bodies; Ischaemic flap; MicroRNAs.

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