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.

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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
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article

Augmentation of peripheral nerve regeneration by hypoxic allogenic Schwann-like cells and secretome in acute nerve injury of Rattus norvegicus

Nur Arfian, Dwikora Novembri Utomo, Ferdiansyah Mahyudin, Damayanti Tinduh et al.
Stem Cell Research & Therapy
Nerve injury and regeneration
article

Augmentation of peripheral nerve regeneration by hypoxic allogenic Schwann-like cells and secretome in acute nerve injury of Rattus norvegicus

Nur Arfian, Dwikora Novembri Utomo, Ferdiansyah Mahyudin, Damayanti Tinduh, Hari Basuki Notobroto, Tito Sumarwoto, Сholahuddin Рhatomy, Muhana Fawwazy Ilyas, Fedik Abdul Rantam, Romaniyanto, Cita Rosita Sigit Prakoeswa, Heri Suroto
article en

Abstract

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.

Stem Cell Research & Therapy
Openalex Percentile: Top 16%
Nerve injury and regeneration
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