Impact of Aging on the Regenerative Properties of Bone Marrow-, Muscle-, and Adipose-Derived Mesenchymal Stem/Stromal Cells

Abstract

Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative therapies due to their multipotency and ready availability, but their application can be complicated by patient-specific factors like age or illness. MSCs have been investigated for the treatment of many musculoskeletal disorders, including osteoarthritis and osteoporosis. Due to the prevalence of these diseases in older populations, researchers have studied how aging affects MSC properties and have found that proliferation and differentiation potential are impaired. However, these effects have never been compared among MSCs isolated from multiple tissue sources in the same, healthy donor. Revealing differences in how MSCs are affected by age could help identify an optimal cell source for musculoskeletal therapies targeting older patients. MSCs were isolated from young and old rabbit bone marrow, muscle, and adipose tissue. Cell yield and viability were quantified after isolation procedures, and expansion properties were assessed using assays for proliferation, senescence, and colony formation. Multipotency was also examined using lineage-specific stains and spectrophotometry of metabolites. Results were compared between age groups and among MSC sources. Results showed that MSCs are differentially influenced by aging, with bone marrow-derived stem cells having impaired proliferation, senescence, and chondrogenic response, whereas muscle-derived stem cells and adipose-derived stem cells exhibited no negative effects. While age reduced overall cell yield and adipogenic potential of all MSC populations, osteogenesis and clonogenicity remained unchanged. These findings indicate the importance of age as a factor when designing cell-based therapies for older patients.

Umbilical cord-derived stem cells (ModulatistTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

“…Although autologous stem cell transplantation holds some advantages, including safety of approach and reduction of virus or disease transmission; it also has disadvantages, namely the uncertainty of stem cell quality. Several studies have shown stem cell quality significantly decreases in older patients, and under certain conditions (Beane et al, 2014;Nakamura et al, 2016). Therefore, allogeneic stem cell therapy is regarded as a considered as suitable alternative to autologous transplantation.…”

“…UCMSCs have also made great strides; unlike adipose tissue and BM, UC contains various compartments of stem cells, such as in cord-lining membrane, Wharton's jelly, cord vein, MODULATIST TM show strong immunomodulation capacity and blood. Studies have shown that MSCs can be successfully isolated from whole UC or from each compartment (Bieback and Netsch, 2016;Lim and Phan, 2014;Raoufil et al, 2015;Watson et al, 2015;Zhang et al, 2011). The isolated MSCs successfully differentiate into various functional cells, including adipocytes, osteoblasts, and chondroblasts, and also successfully transdifferentiate into hepatic-like cells, neuron-like cells, and cardiomyocytes.…”

Adipose Derived Tissue Engineered Heart Valve

“…According to current literature the anatomical site of the adipose tissue does not affect the total number of viable cells that can be obtained from the subcutaneous fatty tissue [32,33]. Compared with mesenchymal stem cells from bone marrow biopsies, ADSC show also no statistically significant correlation between ADSC stem cell quality, proliferation capacity and the patient's age [34]. Additionally, ADSC implicate an equal differentiation potential into cells and tissues of mesenchymal origin [35].…”

Low power laser irradiation and human adipose-derived stem cell treatments promote bone regeneration of critical-sized calvarial defects in rats

“…The extraction of ADSCs is relatively simple, with minimum donor site morbidity. More importantly, compared to other agedependent adult stem cells, such as bone marrow-derived mesenchymal stem cells (BMSCs), the quality and proliferation capacities of ADSCs do not decline with the age of the patient [9][10][11]. ADSCs are therefore a superior cell to other types of adult stem cells as a source for clinical approaches.…”