Researchers demonstrate the potential of using biomaterials-based approach for the controlled release of mesenchymal stem cell (MSC)-secreted neuroprotective factors for protecting against Parkinson’s disease (PD) in vitro.
PD is a multifactorial neurodegenerative disorder, the etiology of which remains largely unknown. The primary clinical feature of the disease is progressive impairment of voluntary motor control, which is caused by a selective degeneration of the dopaminergic neurons. Increase in reactive oxygen species (ROS) resulting in oxidative stress is largely associated with PD.
MSCs are an attractive tool for regenerative medicine due to their self-renewal, multipotency, and immunomodulatory properties. They also hold the ability to secrete products into the culture medium, thus creating a favorable microenvironment for treating neurodegenerative diseases. These products include neuroprotective factors such as cytokines, chemokines and angiogenic molecules, collectively termed as secretome, that accumulate in MSC culture medium. However, long lasting cell-free administration of secretome in vitro or in vivo is challenging.
In the present study published in European Journal of Pharmaceutics and Biopharmaceutics, a team of researchers at Italy’s Mario Negri Institute for Pharmacological Research used the conditioned media from rat adipose tissue-derived MSCs (RAA-MSCs) to evaluate its neuroprotective effect against pro-oxidizing agents such as hydrogen peroxide (H2O2) or the dopaminergic selective toxin 6-hydroxydopamine (6-OHDA) that is commonly used to model PD neurodegeneration.
Results showed that pre-conditioning neuroblastoma cells with 100% RAA-MSC media before treating them with H2O2 and 6-OHDA, decreased the mortality and ROS generation rate in these cells. To achieve long lasting and controlled release of secretome, the team used injectable biodegradable hydrogels that offer a possible in situ implant with mini-invasive techniques. The hydrogels composed of either type I bovine collagen and low-molecular-weight hyaluronic acid or collagen and polyethylene glycol, were suitable for RAA-MSC embedding up to 48 hours. The secretome released from these RAA-MSCs was active and counteracted 6-OHDA toxicity and showed upregulation of the antioxidant enzyme sirtuin 3 in vitro.
Thus, findings from this study provide preliminary evidence to support a biomaterials-based approach for the controlled delivery of MSC-produced neuroprotective factors in treating PD and other neurodegenerative diseases.
Source: Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson’s disease related toxin 6-hydroxydopamine. Chierchia A et al., European Journal of Pharmaceutics and Biopharmaceutics, September 2017. DOI