Evidence map›Paper›PMID 41779050›Full record

ArticleHistochemistry and cell biology2026

Regenerative effects of secretome from tendon-derived stem cells and treadmill training on Achilles tendon healing in rats.

Elahe Maleki, Ayoob Karimizade, Fatemeh Esfandiary, Abbasali Karimpour Malekshah, Mansooreh Mirzaei, Fereshteh Talebpour Amiri

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Article in Histochemistry and cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Elahe MalekiDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Khazar Boulevard, Sari, 4847191971, Iran.ORCID https://orcid.org/0000-0002-8357-7547
Ayoob KarimizadeDepartment of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.ORCID https://orcid.org/0000-0002-5585-0024
Fatemeh EsfandiaryDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Khazar Boulevard, Sari, 4847191971, Iran.ORCID https://orcid.org/0009-0004-2219-8385
Abbasali Karimpour MalekshahDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Khazar Boulevard, Sari, 4847191971, Iran.ORCID https://orcid.org/0000-0002-9649-2235
Mansooreh MirzaeiDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Khazar Boulevard, Sari, 4847191971, Iran. mansoorehmirzaei@yahoo.com.ORCID https://orcid.org/0000-0001-9851-3100
Fereshteh Talebpour AmiriDepartment of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Khazar Boulevard, Sari, 4847191971, Iran. ftaleb2001@yahoo.co.uk.ORCID https://orcid.org/0000-0002-4236-7439

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Achilles tendon ruptures are recognized as one of the most widespread musculoskeletal injuries. Tendon injuries are a notable clinical challenge, primarily due to the restricted regenerative capacity of the tissue and the associated risks of fibrosis and incomplete functional recovery. Recent studies suggest that cell-free therapies, including stem cell-derived secretomes, may facilitate tendon regeneration. Additionally, mechanical stimulation through exercise can enhance tissue remodeling. This study aimed to investigate the combined effects of tendon-derived stem cell (TDSC) secretome and treadmill-based rehabilitation on Achilles tendon regeneration in a rat model. TDSCs were isolated from rat Achilles tendon and characterized using morphology, cytochemical staining, and flow cytometry. In vitro scratch assays were performed to assess cell migration and wound healing in a laboratory setting. The secretome was collected from fourth-passage TDSCs and incorporated into a collagen-based, injectable hydrogel. A total of 42 adult female Wistar rats were categorized into eight distinct experimental groups, including injury-only, treadmill-only, secretome-only, and treadmill + secretome groups. A surgical procedure was performed to induce a partial rupture of the Achilles tendon, followed by the injection of a secretome-loaded hydrogel at the site of injury. Subsequently, a structured treadmill training program was initiated post-surgery. Regenerative outcomes were evaluated using footprint analysis, histological staining (hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome), and biomechanical testing. In vitro scratch assays demonstrated that TDSCs treated with secretome exhibited enhanced migratory capabilities. Flow cytometry confirmed the identity of these mesenchymal stem cells (MSCs). In vivo studies showed that the combination therapy group (secretome-loaded hydrogel and treadmill training) achieved superior histological recovery. This group exhibited organized collagen bundles, aligned spindle-shaped tenocytes, minimal inflammation, and restored extracellular matrix integrity. PAS staining indicated reduced glycosaminoglycan degradation, while Masson's trichrome staining revealed partial collagen maturation. Additionally, footprint analysis showed improved functional performance, with the combination group achieving significantly higher Achilles functional index scores. Biomechanical testing confirmed enhanced tensile strength and elastic modulus, approaching values comparable to those of intact tendon healing. The synergistic application of TDSC-derived secretome along with treadmill training significantly improved tendon regeneration, matrix remodeling, and functional recovery. This cell-free, bioactive approach offers a promising therapeutic alternative for enhancing tendon recovery.

Indexed as

Achilles TendonPhysical Conditioning, AnimalRegenerationSecretomeStem CellsTendon InjuriesWound HealingAnimalsCells, CulturedFemaleRatsRats, WistarAchilles tendon ruptureHealingSecretomeTendon-derived stem cellsTreadmill

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.