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Sasha Bakhru: Functional Polymeric Microcapsules for Neural Stem Cell Expansion

The potential for therapeutic use of early neural progenitors has been realized in recent years. Through preliminary clinical studies involving transplantation of neural stem cells (NSCs) into the brains of patients with Parkinson's disease, clinical researchers have achieved long-lasting symptomatic improvement.

However, a presently unresolved challenge hindering widespread use of such technologies is the inability to achieve timely NSC expansion without loss of multipotency, contributing to a scarcity of NSCs available for patients in need. We hypothesize that a three-dimensional, polymeric hydrogel scaffold incorporating biochemical cues may sufficiently mimic the natural neural stem cell niche to promote NSC self-renewal ex-vivo.

Towards this end, functional polymeric microcapsules fabricated by complex coacervation of methylated collagen (MC) and a synthetic negatively charged terpolymer (TP) of methyl methacrylate (MMA), methacrylate (MAA) and hydroxyethyl methacrylate are used to encapsulate NSCs. Additionally, combinations of soluble signaling molecules (e.g. fibroblast growth factor basic (FGF2), laminin, heparin, and fibronectin) immobilized within the capsular lumen are employed to stimulate NSC self-renewal.

Unlike similar schemes for cellular microencapsulation, the MC/TP system affords substrate functionality through cellular binding domains (RGD) on the polycationic collagen network. Furthermore, the synthetic TP component comprises hydrophobic, hydrophilic and charge carrying blocks, the relative amounts of which are tuned to achieve desired biologically significant materials properties such as porosity/permeability and fixed charge density.

In an effort to controllably and reproducibly fabricate such microcapsules for NSC culture, a novel microcapsule generator has been designed and built. Characterization of NSC expansion efficiency in capsules containing combinations of the above mentioned signaling molecules is underway.

References:

Bjorklund A, Lindvall O. Nature 405 (6789): 892-895, 2000.
Yin C, Chia SM, Quek CH, et al. Biomaterials 24 (10): 1771-1780, 2003.

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Other Articles by Sasha Bakhru:

Sasha Bakhru: Immunofluorescence Staining of NSCs
Sasha Bakhru: Microencapsulation by Complex Coacervation
Sasha Bakhru's Bibliography