Homing of Adipose-Derived Stem Cells to a Tendon-Derived Hydrogel: A Potential Mechanism for Improved Tendon-Bone Interface and Tendon Healing

Austin Franklin; Jung Gi Min; Hiroki Oda; Yukitoshi Kaizawa; Jacinta Leyden; Zhen Wang; James Chang; Paige M Fox

doi:10.1016/j.jhsa.2020.05.003

Homing of Adipose-Derived Stem Cells to a Tendon-Derived Hydrogel: A Potential Mechanism for Improved Tendon-Bone Interface and Tendon Healing

J Hand Surg Am. 2020 Dec;45(12):1180.e1-1180.e12. doi: 10.1016/j.jhsa.2020.05.003. Epub 2020 Jun 27.

Authors

Austin Franklin¹, Jung Gi Min¹, Hiroki Oda¹, Yukitoshi Kaizawa¹, Jacinta Leyden¹, Zhen Wang¹, James Chang¹, Paige M Fox²

Affiliations

¹ Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University Medical Center, Palo Alto, CA; Division of Plastic and Reconstructive Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.
² Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University Medical Center, Palo Alto, CA; Division of Plastic and Reconstructive Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA. Electronic address: pfox@stanford.edu.

PMID: 32605739
DOI: 10.1016/j.jhsa.2020.05.003

Abstract

Purpose: Tendons are difficult to heal owing to their hypocellularity and hypovascularity. Our laboratory has developed a tendon-derived hydrogel (tHG) that significantly improves tendon healing in an animal model. We hypothesized that a potential mechanism for improved healing with tHG is through the attraction of systemic stem cells.

Methods: Homing of systemic adipose-derived stem cells (ADSCs) to tendon injuries was assessed with acute and chronic injury models. Injury sites were treated with saline or tHG, and animals given a tail vein injection (TVI) of labeled ADSCs 1 week after treatment. One week following TVI, rats were harvested for histology. To further evaluate a potential difference in homing to tHG, a subcutaneous injection (SQI) model was used. Rats were treated with an SQI of saline, silicone, ADSCs in media, tHG, tHG + fibroblasts (FBs), or tHG + ADSCs on day 0. One week after SQI, rats underwent TVI with labeled ADSCs. Samples were harvested 2 or 3 weeks after SQI for analysis. Flow cytometry confirmed homing in the SQI model.

Results: Systemically delivered ADSCs homed to both acute tendon and chronic tendon-bone interface (TBI) injury sites. Despite their presence at the injury site, there was no difference in the number of macrophages, amount of cell proliferation, or angiogenesis 1 week after stem cell delivery. In an SQI model, ADSCs homed to tHG. There was no difference in the number of ADSCs homing to tHG alone versus tHG + ADSCs. However, there was an increase in the number of living cells, general immune cells, and T-cells present at tHG + ADSC versus tHG alone.

Conclusions: The ADSCs home to tendon injury sites and tHG. We believe the attraction of additional systemic ADSCs is one mechanism for improved tendon and TBI healing with tHG.

Clinical relevance: Treatment of tendon and TBI injuries with tHG can augment healing via homing of systemic stem cells.

Keywords: Adipose-derived stem cell; hydrogel; mesenchymal stem cell; stem cell homing; stem cell recruitment.

MeSH terms

Adipose Tissue*
Animals
Hydrogels*
Rats
Stem Cells
Tendons
Wound Healing

Substances

Hydrogels