Hydrogel scaffolds are increasingly being used as tissue-mimicking materials and as vehicles to improve transplanted stem cell retention and survival. We have recently developed a new chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method that is able to probe the in vivo stability and gelatin decomposition of implanted composite hyaluronic acid (HA) hydrogels in a ?label-free? fashion. Compared to naked cells, we found that transplanted neural stem cells showed improved survival when hydrogel scaffolding was applied. A major question that remains is the optimal mechanical properties of the hydrogel, and how this relates to cell survival. At the one hand, for initial structural support, the gels should not decompose too fast, but at the other hand they should at some point decompose to allow transplanted cells to grow out and integrate with the surrounding host tissue.
Our aim i s to synthesize a range of composite near- infrared (NIR)-HA hydrogels with different compositions and stabilities, to image their stability properties in vivo, and to correlate the CEST/NIR optical imaging findings with cell survival as assessed using bioluminescent imaging (BLI) as conventional readout. Using supercharged green fluorescent protein (sGFP) as a new CEST MRI bimodal reporter gene, we will also investigate whether or not CEST MRI is able to probe in vivo cell survival simultaneously. We have chosen to apply this approach to transplantation of glial-restricted precursor cells (GRPs) in a transgenic amyotropic lateral sclerosis (ALS) mouse model, as we have found that transplanted naked cells without hydrogel scaffolding survive poorly in the hostile ALS tissue environment.
Hydrogels are materials that resemble some of the properties of body tissue. When stem cells are embedded within hydrogels before they are transplanted, they often survive longer. We will use a special MRI technique to interrogate the stability of the hydrogels, and see how this correlates to transplanted cell survival in a mouse model of Lou Gehrig's disease.
|Srivastava, Rohit K; Bulte, Jeff W M; Walczak, Piotr et al. (2018) Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men. Glia 66:907-919|
|Bulte, Jeff W M; Daldrup-Link, Heike E (2018) Clinical Tracking of Cell Transfer and Cell Transplantation: Trials and Tribulations. Radiology 289:604-615|