组织科学与工程学报

Advanced Donor Age Impairs Bone Marrow Cell Therapeutic Efficacy for Cardiac Disease

Abstract

Xiaoyin Wang,Junya Takagawa,Daniel J. Haddad,Kranthi Pinnamaneni,Yan Zhang, Richard E. Sievers, William Grossman,Yerem Yeghiazariansand Matthew L. Springer

Therapeutic results of clinical autologous bone marrow cell (BMC) therapy trials for cardiac disease have been modest compared to results of BMC implantation into rodent hearts post-myocardial infarction (MI). In clinical trials, autologous BMCs are typically harvested from older patients who have recently suffered an MI. In contrast, experimental studies in rodent models typically utilize donor BMCs isolated from young, healthy, inbred mice that are not the recipients. Using unfractionated BMCs from donor mice at ages of young, middle-aged, and old, we discovered that recipient left ventricular function post-MI was significantly improved by young donor BMC implantation but was only preserved by middle-aged donor BMCs. Notably, old donor BMCs did not slow the decline in recipient post-MI cardiac function, suggesting BMC impairment by advanced donor age. Furthermore, we also show here that BMCs that are therapeutically impaired by donor age can be further impaired by concurrent donor MI. In conclusion, our findings suggest that therapeutic impairment of BMCs by advanced age is one of the important factors that can limit the success of clinical autologous BMC-based therapy