Tracking of normoxic and hypoxic pretreated adult human mesenchymal stem cells in association with strokeutilizing 1H and 23Na at ultra-high magnet field MRI

J.T. Rosenberg, K. Sellgren, F. Calixto Bejarano, M. Baird, M.W. Davidson, T. Ma & S.C. Grant

NHMFL and The Florida State University

Supported by AHA Grant-in-Aid to Teng Ma & Samuel Grant

Cell therapy is being evaluated as a potential treatment for ischemic stroke. Hypoxic pretreated hMSCs have show increased resistant to ischemic stroke environment and added therapeutic properties.

In this in vivo study, normoxic and hypoxic cultured hMSCs were labeled with a fluorescent micron sized iron oxides (MPIOs) and injected intra-arterially to treat ischemic stroke resulting from a middle cerebral artery occlusion (MCAO). Serial MRI at 21.1 T was performed to acquire 1H and 23Na images of lesion progression, cell migration & longitudinal contrast.

Facilities: 900-MHz UWB NMR Magnet, Tallahassee, FL

Citation: Rosenberg, J.T., Sellgren, K., Bejarano, F.C., Baird, M., Davidosn, M., Teng, M., Grant, S.C., Tracking of normoxic and hypoxic pretreated human Mesenchymal Stem cells in association with stroke utilizing 1H and 23Na at ultra-high magnet field MRI. Stroke, In preparation

Methods

Results

Conclusions:• Significant clearance of hSMCs with in 1 week• T2W and 23Na images show lesion size recovery

High field 23Na imaging appears to be a more sensitive indicator of physiological effects of MSC therapy on stroke lesion recovery

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T2- weighted image

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Middle cerebral artery occlusion (MCAO):-- following Longa et al (1989) and Uluç et al (2011)

• Male Sprague Dawley rats weighing •1-hr occlusion following re-perfusionIntra-arterial injection of hMSCs:• 1 millions cells labeled with MPIO into intracarotid artery • MRI at 24 and 1 week following surgery

MR equipment for in vivo experiments:• 21.1-T UWB vertical magnet• Double tuned 1H and 23Na 33-mm RF birdcage coilin vivo imaging protocols:• Stroke assessment: 2D T2 weighted Spin echo (SE)• Labeled cells: 3D gradient recalled echo (GRE)• Sodium in stroke: 3D 23Na GRE

Percent decrease: 47.8 % 74.2 %

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Segmented stroke lesion (yellow)

T2- weighted image

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Segmented stroke lesion (purple)

23Na image

Percent decrease in stroke lesion area for 1H and 23Na images

23Na only shows significant difference in stroke recovery