Bone Marrow–Derived Mesenchymal Stem Cells Transduced With Scleraxis Improve Rotator Cuff Healing in a Rat Model

Abstract

Biologic augmentation of acutely injured rotator cuffs with Scx-transduced MSCs may improve rotator cuff tendon healing and reduce the incidence of re-tears. However, further studies are needed to determine if this remains safe and effective in larger models.

The Effect of Granulocyte-colony Stimulating Factor on Rotator Cuff Healing After Injury and Repair

“…Although no MSC-related orthopaedic treatment is, to date, approved for clinical use in the United States, some previous laboratory studies have demonstrated the potential of MSCs to improve tendon-to-bone healing in vivo [19][20][21]33]. Despite the promise of MSCs, there are significant technical and regulatory hurdles that have precluded their widespread clinical adoption.…”

“…Gulotta et al reported that transplanted allogenic MSCs did not improve the quality or strength of rotator cuff healing despite evidence of retention and metabolic activity [19]. Further studies assessed the effect of genetically modified allogeneic stem cells on rotator cuff repair, first examining the effect of allogenic MSCs treated with adenovirus-associated MT1-MMP [20] and also BMP-13 [21]. Cells overexpressing MT1-MMP demonstrated moderate increases in enthesis metachromasia, whereas ad-BMP-13 demonstrated no histologic improvement.…”

“…Cells overexpressing MT1-MMP demonstrated moderate increases in enthesis metachromasia, whereas ad-BMP-13 demonstrated no histologic improvement. A followup study showed that transducing allogeneic, marrow-derived MSCs with scleraxis improved the amount of fibrocartilage present at the tendon-bone interface at the 4-week time point [21]. Hernigou et al presented a case series of 45 human patients who underwent arthroscopic rotator cuff surgery augmented with a heterogenous population of stem and progenitor cells taken from intraoperative iliac crest marrow aspirates [24].…”

“…Under an Institutional Animal Care and Use Committeeapproved protocol, 52 mature, female Sprague-Dawley rats received a surgically created, full-thickness supraspinatus tendon defect followed by surgical repair, as previously described [3,4,13,[19][20][21]. The left shoulder was approached through a deltoid-splitting technique.…”

“…In an effort to improve tendon-to-bone healing after rotator cuff repair, numerous biologic-and tissue engineering-based techniques have been used, including use of anabolic growth factors [23,25], proteinase inhibitors [3,4] as well as augmentation with stem and progenitor cell populations [19,21,33]. Mesenchymal stem cells (MSCs) are natively involved in tissue maturation, healing, and remodeling [43] and, as a result of their migratory, multipotent, and immunomodulatory properties, possess the potential for regenerating a wide range of pathologic or degenerative tissues.…”