Stem Cells Genetically Modified With the Developmental Gene MT1-MMP Improve Regeneration of the Supraspinatus Tendon-to-Bone Insertion Site

Abstract

Biologic augmentation of repaired rotator cuffs with MT1-MMP-transduced MSCs may reduce the incidence of retears. However, further studies are needed to determine if this remains safe and effective in larger models.

Effect of Immediate and Delayed High-Strain Loading on Tendon-to-Bone Healing After Anterior Cruciate Ligament Reconstruction

“…However, following ligament reconstruction or tendon repair, the structure and composition of the graft attachment site are replaced by disorganized scar. The global hypothesis of our laboratory's ongoing work is that, while initial healing depends on biological signals such as cytokines 12,[18][19][20][21] , mechanical load is of paramount importance for subsequent remodeling of the healing attachment site.…”

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.…”

“…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.…”

Large/Massive Tears, Fatty Infiltration, and Rotator Cuff Muscle Atrophy: A Review Article With Management Options Specific to These Types of Cuff Deficiencies

“…These a broadly categorised to modalities to improve the repair site/tendon-to-bone healing environment and bridging techniques across large tears. Repair site augmentation options include gene therapy, stem cells, growth factors, transcription factors and platelet rich plasma (PRP) (65)(66)(67)(68)(69)(70)(71)(72)(73)(74). Studies into these options are still on-going with most results based on animal-research models.…”