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

Abstract

Successful tissue engineered repair in the aging adult requires an abundant source of autologous, multipotent mesenchymal stem cells (MSCs). Although the number of bone marrow-derived MSCs declines dramatically with aging, their effectiveness in repair with increasing age has not been studied. We tested the hypothesis that MSCs harvested from geriatric rabbits would not repair patellar tendon defects as well as MSCs harvested from younger adult rabbits. In a novel within-subjects experiment, autologous MSCs were isolated from I-year old rabbits, culture expanded, and cryogenically preserved. After housing the rabbits for 3 years, MSCs were re-harvested from the 4-year old rabbits and expanded. Five hundred thousand thawed and fresh MSCs were each separately mixed with type I collagen gel (333.3 x lo3 cells/mg collagen) 24 h before surgery, and the resulting constructs implanted in bilateral full-length central third tendon defects. Twelve weeks post-surgery, the bone-tendon repair-bone units were failed in tension. Intra-animal (paired) comparisons between repair tissue treated with 1-year old MSCs and repair tissue treated with 4-year old MSCs resulted in no significant differences (ct = 0.051 in material properties including maximum stress (10.8 MPa vs. 9.9 MPa; p = 0.762), modulus (139.8 MPa vs. 146.2 MPa; p = 0.914), and strain energy density (0.52 N d m m ' vs. 0.53 Nmndmm'; p = 0.966). Despite an age-related trend, there were also no significant differences in structural properties including maximum force (62.9 N vs. 27.0 N; p = 0.070), stiffness (24.9 Nlmm vs. 12.0 N/mm; p = 0.11 l), and strain energy (87.2 Nmm vs. 31.4 Nmm; p = 0.061). A subset of the rabbits (n = 4 1 yrMSC, n = 2 4 yrMSC) showed the presence of ectopic bone in the repair region and were not included in the mechanical analyses. We conclude that in the rabbit model MSCs do not lose their benefit as a tendon repair therapy with aging and that MSCs can be cryogenically stored for 3 years and still effectively repair soft tissue injuries.

Use of a bioscaffold to improve healing of a patellar tendon defect after graft harvest for ACL reconstruction: A study in rabbits

“…13,14,30,31 In the current study, only the structural properties of the bone-neo-PT-bone complex were measured, i.e., without the contribution from the remaining PT tissue. Nevertheless, other studies have isolated the neo-PT in a similar fashion, 15,16,32 and our data were confirmed by comparing to structural properties obtained by Awad et al Due to the study design, normalization of the parameters representing the structural properties of the SIS-treated and nontreated groups by the sham-operated controls may introduce bias. However, since no statistically significant differences were detected between the sham-operated controls, normalization does not appear to significantly favor either treatment group.…”

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

“…Most experiments, including recently published studies, have been conducted using MSCs isolated primarily from bone marrow aspirates by their tight adherence to plastic dishes, as described by Friedenstein et al (27) 35 years ago, which means that cellular immunotherapy would require a longer-term culture for MSC expansion. Although stem cells have the ability to continuously proliferate and differentiate (develop) into various other types of cells/tissues, several studies still demonstrated that long-term expansion impaired the telomere length and activity of telomerase, in turn leading to senescence of MSCs and damaging their multilineage potential (28)(29)(30)(31). However, the effects of long-term in vitro amplification on the immunological properties of MSCs remain unknown.…”

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

“…Regardless, aged MSCs can produce functional repair tissue. Rabbit tendon injuries repaired with autologous MSCs from young or aged animals produced repair tissue with equivalent material properties [16]. The literature is conflicting whether osteogenic and adipogenic MSC differentiation is agedependent, with some studies suggesting it is independent of age [42,46,49] and others dependent on age [14,30].…”