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Evaluating mesenchymal stem cells derived from young and old cats

Zajic LB, Webb TL, et al. Comparison of proliferative and immunomodulatory potential of adipose-derived mesenchymal stem cells from young and geriatric cats.J Feline Med Surg.2017 Oct;19(10):1096-1102. 

Veterinary medicine is seeing an increasing therpeutic use of adipose-derived mesenchymal stem cells (MSCs) in general and specialty regenerative medicine practices.  Winn Feline Foundation has funded a number of cat health studies for various disorders (kidney disease, asthma, inflammatory bowel disease, gingivostomatitis and heart disease) that evaluate the safety and efficacy of MSCs in cats. The use for degenerative joint disease (arthritis) is more common yet not as frequent in cats as in other species such as horses and dogs.

MSCs have the potential for benefit due to their direct regenerative properties and also their ability to alter the surrounding tissue environment through paracrine  (def: a substance secreted by a cell and acting on adjacent cells). In addition in the disease conditions previously mentioned, MSCs provide anti-inflammatory properties. MSC’s immunomodulatory effects include suppression of lymphocyte proliferation in vitro, decreased production of tumor necrosis factor alpha and interleukin (IL)-6 by stimulated macrophages, decreased production of IL-12 by dendritic cells (DCs) and suppression of DC function.

Using autologous (a cat’s own cells) MSCs for therapy in older animals requires harvesting adipose (fat) tissue from cats that may be chronically ill. The authors note that in their experience adipose-derived MSCs from geriatric patients have been difficult to grow. Therefore, the aim of this study was to explore the possible effects of donor age on the functional properties (i.e. proliferate in culture, suppress lymphocyte proliferation and undergo senescence) of feline adipose MSCs.

The investigators collected adipose tissues from five young (< 5 years) and six geriatric (>10 years) cats that were cryopreserved for subsequent adipose MSC isolation and culture.

The results of the study found that adipose-derived MSCs from geriatric cats (median 11 days, range 9-22 days) took significantly longer to reach passage 2 (P2) compared to aMSCs from young healthy cats (median 7 days, range 6-8 days).  It was noted that the two geriatric cats that took the longest time to passage 2 both had serum creatinine > 2mg/dl. Although aMSCs from geriatric cats were significantly slower to reach P2, their ability to suppress T-lymphocyte activation and proliferation was equivalent to those aMSCs from younger cats.

Therefore, even though the efficacy of autologous aMSCs from aging cats does not appear to decrease with age, the investigators state the ability to produce enough cells in a timely manner for clinical therapeutic use may be inadequate in geriatric patients.  (VT)

See also:
Quimby JM, Webb TL, et al. Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies. Stem Cell Res Ther. 2013 Apr 30;4(2):48.