2. Academic Validation
  3. IGFBP3 enhances adipose-derived stem cell function in soft tissue injury repair via ITGB1 and ERK pathway activation

IGFBP3 enhances adipose-derived stem cell function in soft tissue injury repair via ITGB1 and ERK pathway activation

  • Cell Biol Toxicol. 2025 May 15;41(1):85. doi: 10.1007/s10565-025-10024-8.
Sirui Tian 1,  Haiyang Yu 2,  Ruoxuan Yang 1,  Heshi Wang 1,  Baohong Zhao 1,  Danning Wang 3
Affiliations

Affiliations

  • 1 Department of Oral Implantology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, No. 117 Nanjing North Street, Heping District, Shenyang, 110002, Liaoning Province, China.
  • 2 Comprehensive Emergency Department, Shenyang Stomatological Hospital, Shenyang, 110002, Liaoning, China.
  • 3 Department of Oral Implantology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, No. 117 Nanjing North Street, Heping District, Shenyang, 110002, Liaoning Province, China. dnwang@cmu.edu.cn.
PMID: 40369223 DOI: 10.1007/s10565-025-10024-8
Abstract

Soft tissue injury (STI) is a prevalent condition that requires effective therapeutic approaches. The focus of this investigation was to elucidate the molecular mechanisms linked to the IGFBP3 protein in adipose-derived stem cells (ADSCs) for STI repair, utilizing single-cell multiomics technology and a 3D bioprinting model. Establishment of a mouse-based STI model facilitated the comparison of cellular compositions and communication variances between wounded and normal tissues through single-cell RNA Sequencing (scRNA-seq). High-throughput transcriptomics and bioinformatics analysis pinpointed IGFBP3 as a key target in ADSCs related to STI repair. In vitro experiments assessed IGFBP3's effects on ADSCs' epithelial cell differentiation, proliferation, and migration using various assays and lentivirus transfection to manipulate IGFBP3 expression. A 3D bioprinting technique was used to create an ADSCs-IGFBP3 peptide self-assembling hydrogel scaffold, characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, SEM, and TEM. The scaffold's efficacy was validated in an animal model. Results showed nine cell subtypes in both normal and injured tissues, with increased ADSCs in STI tissues exhibiting enhanced connectivity and interactions. RNA-seq analysis confirmed IGFBP3 as crucial for ADSCs and STI. In vitro and 3D bioprinting experiments, along with animal model validation, confirmed IGFBP3's role in STI repair. Upregulation of IGFBP3 in ADSCs promoted epithelial cell differentiation by enhancing ITGB1 expression, activating the ERK pathway to boost cell proliferation and migration. This study highlights IGFBP3's significant role in ADSCs for STI repair, providing potential molecular targets for developing new treatments. The findings offer valuable insights into IGFBP3's mechanisms, aiding in advancing STI therapeutic strategies.

Keywords

3D bioprinting; Adipose-derived stem cells; Epithelial cell differentiation; IGFBP3 protein; Single-cell multiomics; Soft tissue injury.

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