A biocompatible and injectable hydrogel to boost the efficacy of stem cells in neurodegenerative diseases treatment

一种生物相容性可注射水凝胶,可增强干细胞在神经退行性疾病治疗中的功效

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作者:Helena Ferreira, Diana Amorim, Ana Cláudia Lima, Rogério P Pirraco, Ana Rita Costa-Pinto, Rui Almeida, Armando Almeida, Rui L Reis, Filipa Pinto-Ribeiro, Nuno M Neves

Aims

Stem cell therapies emerged as treatment modalities with potential to cure neurodegenerative diseases (NDs). However, despite high expectations, their clinical use is still limited. Critical issues in treatment outcomes may be related to stem cells formulation and administration route. We develop a hydrogel as a cell carrier, consisting of compounds (phospholipids and hyaluronic acid-HA) naturally present in the central nervous system (CNS). The HA-based hydrogel physically crosslinked with liposomes is designed for direct injection into the CNS to significantly increase the bone marrow mesenchymal stem cells (BMSCs) bioavailability. Materials and

Methods

Hydrogel compatibility is confirmed in vitro with BMSCs and in vivo through its intracerebroventricular injection in rats. To assess its efficacy, the main cause of chronic neurologic disability in young adults is selected, namely multiple sclerosis (MS). The efficacy of the developed formulation containing a lower number of cells than previously reported is demonstrated using an experimental autoimmune encephalomyelitis (EAE) rat model. Key findings: The distribution of the engineered hydrogel into corpus callosum can be ideal for NDs treatment, since damage of this white matter structure is responsible for important neuronal deficits. Moreover, the BMSCs-laden hydrogel significantly decreases disease severity and maximum clinical score and eliminated the relapse. Significance: The engineering of advanced therapies using this natural carrier can result in efficacious treatments for MS and related debilitating conditions.

Significance

The engineering of advanced therapies using this natural carrier can result in efficacious treatments for MS and related debilitating conditions.

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