Augmentation of peripheral nerve regeneration by hypoxic allogenic Schwann-like cells and secretome in acute nerve injury of Rattus norvegicus
Abstract Background This study evaluated whether hypoxia-conditoned allogeneic Schwann-like cells (SLCs) or their secretome augment peripheral nerve regeneration after acute sciatic nerve injury in rats by assessing biologic and functional outcomes. Methods In this in-vivo experiment, Wistar rats (Rattus norvegicus) underwent sciatic nerve transection and repair and were assigned to control (suture only), hypoxic allogeneic SLC, or hypoxic SLC-secretome groups. SLCs were generated from adipose-derived mesenchymal stem cells using the Kingham protocol with 10% platelet-rich plasma and 1% hypoxic preconditioning. HIF-1α was evaluated by immunohistochemistry; TGF-β and VEGF by ELISA; CD-31, NCAM, α-SMA, and NeuN by qRT-PCR at weeks 3 and 6; and motor recovery by sciatic function index (SFI) from weeks 0–6. Results HIF-1α staining was stronger in both intervention groups than in controls and was more prominent at week 6 than week 3. At week 3, three-group differences were significant for TGF-β ( p =0.002), α-SMA ( p <0.001), CD-31 ( p =0.003), NCAM ( p <0.001), and NeuN ( p =0.050), but not VEGF ( p =0.235). At week 6, TGF-β, α-SMA, CD-31, NCAM, and NeuN all differed significantly (all p <0.001), whereas VEGF remained non-significant ( p =0.323). From week 2 to week 6, SFI differed significantly among groups (all p ≤0.001), with both interventions outperforming control; the secretome group showed the strongest recovery trend. Conclusion In this acute rat PNI model, hypoxic-conditioned allogeneic SLCs and their secretome were associated with improved motor recovery (higher SFI) and a biomarker profile consistent with a more supportive repair environment (higher TGF-β, HIF-1α/NCAM/CD-31; lower α-SMA) versus suturing alone. These findings are associative and do not establish causality.
Authors
- Nur Arfian (ORCID: https://orcid.org/0000-0003-1694-2054)
- Dwikora Novembri Utomo (ORCID: https://orcid.org/0000-0002-7832-5695)
- Ferdiansyah Mahyudin (ORCID: https://orcid.org/0000-0001-8757-9251)
- Damayanti Tinduh (ORCID: https://orcid.org/0000-0001-6604-8152)
- Hari Basuki Notobroto (ORCID: https://orcid.org/0000-0002-3905-7413)
- Tito Sumarwoto (ORCID: https://orcid.org/0000-0002-1403-6667)
- Сholahuddin Рhatomy (ORCID: https://orcid.org/0000-0002-5512-6706)
- Muhana Fawwazy Ilyas (ORCID: https://orcid.org/0000-0002-0176-9773)
- Fedik Abdul Rantam (ORCID: https://orcid.org/0000-0002-1047-2410)
- Romaniyanto (ORCID: https://orcid.org/0000-0002-4175-1439)
- Cita Rosita Sigit Prakoeswa (ORCID: https://orcid.org/0009-0000-0680-5545)
- Heri Suroto
Publication Details
- Journal
- Stem Cell Research & Therapy
- Published
- 2026-09-16
- DOI
- https://doi.org/10.1186/s13287-026-05274-0
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 0.00