Regeneration of a full-thickness defect in rotator cuff tendon with umbilical cord-derived mesenchymal stem cells in a rat model

Abstract

Although rotator cuff disease is a common cause of shoulder pain, there is still no treatment method that could halt or reveres its development and progression. The purpose of this study was to investigate the efficacy of umbilical cord-derived mesenchymal stem cells (UC MSCs) on the regeneration of a full-thickness rotator cuff defect (FTD) in a rat model. We injected either UC MSCs or saline to the FTD and investigated macroscopic, histological and biomechanical results and cell trafficking. Treatment with UC MSCs improved macroscopic appearance in terms of tendon thickness at two weeks, and inflammation, defect size, swelling/redness and connection surrounding tissue and slidability at four weeks compared to the saline group. Histologically, UC MSCs induced the tendon matrix formation recovering collagen organization, nuclear aspect ratio and orientation angle of fibroblast as well as suppressing cartilage-related glycosaminoglycan compared to saline group at four weeks. The UC MSCs group also improved ultimate failure load by 25.0% and 19.0% and ultimate stress by 27.3% and 26.8% at two and four weeks compared to saline group. UC MSCs labeled with PKH26 exhibited 5.3% survival at four weeks compared to three hours after injection. This study demonstrated that UC MSCs regenerated the FTD with tendon tissue similar properties to the normal tendon in terms of macroscopic, histological and biomechanical characteristics in a rat model.

Allogenic Umbilical Cord Tissue for Rotator Cuff Injuries

“…The regenerated tendon showed macroscopic, histologic, and biochemical features similar to the native tendon. This study demonstrated that direct injection of UC-MSC led to enhanced healing of FT defects in this animal model, but further experiments must be conducted on larger animal models before any definitive conclusions can be made for human use of this biological 18 …”

“…The dUC-WJ-KGN scaffold improved chondrogenic differentiation and fibrocartilaginous tissue repair from the released KGN cartilage inducer, enabling better functional recovery 28 . Yea and colleagues performed 2 similar experiments using nonfrozen UC-MSCs and freshly T-UC-MSCs to regenerate FT rotator cuff defects 17,18 . The first study using regular UC-MSCs resulted in 5 main findings: The UC-MSC group returned statistically better macroscopic and histologic scores.…”

Regeneration of Chronic Rotator Cuff Tear in a Rabbit Model: Synergetic Benefits of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells, Polydeoxyribonucleotides, and Microcurrent Therapy

“…These characteristics may contribute to UCB-MSCs being a better therapeutic option than other adult MSCs [ 7 ]. Previous studies have demonstrated that UCB-MSCs regenerated full-thickness defects in rotator cuff tendon (full thickness RCTT (FTRCTT)) of rat and rabbit models [ 8 – 10 ]. Recently, there has been a study suggesting deoxyribonucleotide polymers mixed with a chain length between 50 and 2,000 bp; i.e., polydeoxyribonucleotide (PDRN) had effect on the treatment of chronic rotator cuff disease [ 11 ].…”

Exosomes isolated from melatonin-stimulated mesenchymal stem cells improve kidney function by regulating inflammation and fibrosis in a chronic kidney disease mouse model

“… 5 , 6 The paracrine effect of MSCs is also known to not only induce tissue regeneration without fibrosis, but also to inhibit inflammation. 4 , 6 , 7 However, the use of MSCs is associated with some risks because they can induce immune rejection responses and differentiate into cells other than those intended, especially tumor cells. 7 , 8 Moreover, the engraftment rate of cells after MSC transplantation is low.…”

“… 4 , 6 , 7 However, the use of MSCs is associated with some risks because they can induce immune rejection responses and differentiate into cells other than those intended, especially tumor cells. 7 , 8 Moreover, the engraftment rate of cells after MSC transplantation is low. 9 Therefore, another promising approach using MSCs is required to overcome these drawbacks.…”