Autologous Mesenchymal Stem Cell-Mediated Repair of Tendon

Abstract

Mesenchymal stem cells (MSCs) were isolated from bone marrow of 18 adult New Zealand White rabbits. These cells were culture expanded, suspended in type I collagen gel, and implanted into a surgically induced defect in the donor s right patellar tendon. A cell-free collagen gel was implanted into an identical control defect in the left patellar tendon. Repair tissues were evaluated biomechanically (n = 13) and histomorphometrically (n = 5) at 4 weeks after surgery. Compared to their matched controls, the MSC-mediated repair tissue demonstrated significant increases of 26% (p < 0.001), 18% (p < 0. 01), and 33% (p < 0.02) in maximum stress, modulus, and strain energy density, respectively. Qualitatively, there appeared to be minor improvements in the histological appearance of some of the MSC- mediated repairs, including increased number of tenocytes and larger and more mature-looking collagen fiber bundles. Morphometrically, however, there were no significant left-right differences in nuclear aspect ratio (shape) or nuclear alignment (orientation). Therefore, delivering a large number of mesenchymal stem cells to a wound site can significantly improve its biomechanical properties by only 4 weeks but produce no visible improvement in its microstructure.

Effects of age on the repair ability of mesenchymal stem cells in rabbit tendon

“…I). The rabbit patellar tendon was chosen to investigate the effects of MSC aging because of our extensive experience with this model system in studies of repair and in vivo force measurement [3,4,17,31]. Furthermore, the 4-year old age group represents a geriatric state in rabbits as evidenced by a 50% population mortality rate and has been used previously in other investigations into age-related effects on tendon and ligament [17, 43,59].…”

“…Differentiation along these cellular lineages depends on the interaction of local cues from surrounding cells and extracellular matrix as well as the genomic potential of the cells [13]. When harvested from bone marrow, MSCs can be selected through specific culture conditions [37] and isolated from other bone marrow cells without losing their multipotentiality [3,4,8,30,60].…”

“…Our laboratory and others have used bone marrow-derived MSCs for tendon repair in the adolescent or young skeletally mature animal [3,4,47,53,601. Compared to controls, MSC-based tendon repair biomechanics and histology are improved in the Achilles [47,60], patellar [3,4], and flexor tendon models [53]. Despite the advantages that MSCs provide in the young adult repair model, no studies exist investigating their use in geriatric animals.…”

Therapeutic potential of genetically modified mesenchymal stem cells

“…9 Mesenchymal stem cells can also be differentiated into neurons, astrocytes, tenocytes, skeletal myocytes and cells of visceral mesoderm (endothelial cells). [10][11][12][13][14] Bone targeting of culture-expanded murine MSC by ectopic expression of murine a4 integrin Despite the potential of MSC in tissue regeneration, a major limitation remains in the delivery of ex vivo modified MSC to target tissues upon autologous transfer. In our recent study, we have shown that ectopic expression of a4 integrin on mouse MSC resulted in significant increase in bone specific retention of transplanted mouse MSC.…”

Microfabrication of an asymmetric, multi-layered microdevice for controlled release of orally delivered therapeutics

“…Orally delivered pH sensitive hydrogels, in the form of spherical particles, have been used to diffuse therapeutic proteins, such as insulin, directly into the gastrointestinal tract 5,18 . The micropatterning of hydrogels, outside of spherical forms, has been accomplished through photoreaction injection 20,21 , photolithography [21][22][23] , microfluidic patterning24 -26 and micro-molding27 , 28. Hydrogels have been photolithographically added to many lab-ona-chip type devices, combining the hydrogel polymer with silicon or other polymers, such as SU-8.…”