Autologous Adipose Micro-Grafts – A New Tendon Healing Strategy?

Review of "Adipose Micro-Grafts Enhance Tendinopathy Healing in Ovine Model: An In Vivo Experimental Perspective Study" from STEM CELLS Translational Medicine by Stuart P. Atkinson

Previous studies in animal models provided evidence of the therapeutic relevance of the stromal vascular fraction (SVF) of human subcutaneous adipose tissue in tendon healing, thanks in part to the pro-regenerative and anti-inflammatory function of adipose-derived mesenchymal stem cells [1]. Furthermore, related research also supported the development of SVF-based therapies as a potentially effective therapy for Achilles tendinopathy in humans [2, 3].

A recent STEM CELLS Translational Medicine article led by Francesco De Francesco (AOU "OspedaliRiuniti" di Ancona, Ancona, Italy) reports on their application of autologous adipose micro-grafts [4, 5] as a means to promote healing, functionality, and the recovery of tendon structure in model sheep through the intrinsic anti-inflammatory activity of this adipose-derived product [6]. Overall, Palumbo Piccionello et al. describe autologous adipose micro-grafts as a safe and effective treatment for tendinopathy in sheep, which supports the application of this cell therapy to human tendinopathy.

Fifteen days after injecting both common calcaneal tendons of sixteen sheep between the ages of two and five years with collagenase to induce tendinopathy, the authors treated one tendon with autologous adipose micro-grafts and compared this to the non-treated tendon. Encouragingly, tendons receiving autologous adipose micro-grafts possessed characteristics similar to a healthy tendon (e.g., adequate tendon rigidity), and the treated animals displayed significant clinical improvements in terms of lameness relief and function restoration. Overall, compared to the untreated injured tendon, autologous adipose micro-grafts significantly induced repair/regeneration.

Histological analysis of the autologous micro-graft-treated tendons established a significant improvement in fiber orientation and edema and reduced inflammation and necrosis compared to the non-treated injured tendon. These findings suggested that the maintenance and induction of tendon fiber organization lay behind autologous micro-graft-induced tendon repair, thanks to the release of anti-inflammatory and immunomodulatory factors. These improvements correlated with the increased expression of collagen I and Factor VIII and the reduced expression of collagen III at both the protein and mRNA level, suggesting a positive impact of autologous adipose micro-grafts on matrix composition in the treated tendons and improved neo-angiogenesis within lesion sites.

Overall, the authors provide robust evidence that autologous adipose micro-grafts represent a safe and efficient therapeutic approach to improved tendon healing; however, they also note the limited sample size employed in this study.

For more on the reparative and regenerative potential of autologous adipose micro-grafts in tendon healing, stay tuned to the Stem Cells Portal!

References

1. De Francesco F, Ricci G, D'Andrea F, et al., Human Adipose Stem Cells: From Bench to Bedside. Tissue Engineering Part B: Reviews 2015;21:572-584.
2. Albano D, Messina C, Usuelli FG, et al., Magnetic resonance and ultrasound in Achilles tendinopathy: Predictive role and response assessment to platelet-rich plasma and adipose-derived stromal vascular fraction injection. European Journal of Radiology 2017;95:130-135.
3. Usuelli FG, Grassi M, Maccario C, et al., Intratendinous adipose-derived stromal vascular fraction (SVF) injection provides a safe, efficacious treatment for Achilles tendinopathy: results of a randomized controlled clinical trial at a 6-month follow-up. Knee Surgery, Sports Traumatology, Arthroscopy 2018;26:2000-2010.
4. Shen H, Kormpakis I, Havlioglu N, et al., The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing. Stem Cell Research & Therapy 2016;7:144.
5. Hiroshi M, The Potential for Treatment of Skeletal Muscle Disorders with Adipose-Derived Stem Cells. Current Stem Cell Research & Therapy 2010;5:133-136.
6. Palumbo Piccionello A, Riccio V, Senesi L, et al., Adipose micro-grafts enhance tendinopathy healing in ovine model: An in vivo experimental perspective study. STEM CELLS Translational Medicine 2021;10:1544-1560.