Objective: Evaluate the survival and potential of brain-derived progenitor cells as a cell-based therapy(CBT) for Parkinson’s disease in a mouse xenograft and syngeneic rat model.

Background: Brain biopsies from living PD patients, taken during deep brain stimulation surgery, can yield large numbers of progenitor cells with key merits of being both host- and brain-derived progeny (Xu et al., 2013). Interestingly, these brain-derived progenitor cells express a broad array of neurotrophic factors (NTFs) that include the most promising and potent cytoprotective agents against PD neurodegeneration. The colocalization of multiple NTFs (e.g., GDNF, BDNF, CDNF) with progenitor and neural proteins raises the intriguing prospect that BDPCs may effectively integrate into the brain to confer broad and enduring therapeutic function in PD, but a preclinical transplant models are a necessary step to evaluate this potential.

Methods: Human BDPCs were xenografted into immunocompromised NSG mice and Fischer rat BDPCs transplanted into syngeneic rodents. Before transplantation both cell populations were transduced to express a fluorescent luciferase construct and labelled with the iron oxide contrast agent, Molday ION Rhodamine-B™ (MIRB). The MIRB allowed in vivo BDPC tracking using a 3T MRI unit, in addition to bioluminescence imaging(BLI) via the luciferase reaction. Imaging data was correlated with histological findings to ascertain the accuracy and sensitivity of the two tracking modalities, as well as the long-term survival of the BDPCs in vivo.

Results: Xenografted human BDPCs in a pilot cohort of NSG mice show a persistent stable BLI signal and MRI signal void for 6 weeks. Fischer rat syngeneic grafts also showed a robust BLI signal for 2 weeks and were easily localized on MRI. Histological examination of both groups revealed expression of the transduced fluorescent tag highly colocalized with the MIRB tracking agent.

Conclusions: Human BDPCs may provide a novel substrate for personalized CBT in neurological disease. This work provides novel insight into the viability of BDPCs from living PD patients in a xenograft model and from rodents in a syngeneic model. It also offers the key advantage of using brain tissue from living PD patients and has potential to provide unparalleled contributions that expand the field of cellular imaging of the brain and the development of personalized therapeutics for PD.

References: Xu H, Belkacemi L, Jog M, Parrent A, Hebb MO. Neurotrophic factor expression in expandable cell populations from brain samples in living patients with Parkinson’s disease. FASEB J. 2013;27(10):4157-4168. doi:10.1096/fj.12-226555.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/preclinical-evaluation-of-a-novel-autologous-substrate-for-cell-based-therapy/