A Biological Global Positioning System: Considerations for Tracking Stem Cell Behaviors in the Whole Body

Abstract

Many recent research studies have proposed stem cell therapy as a treatment for cancer, spinal cord injuries, brain damage, cardiovascular disease, and other conditions. Some of these experimental therapies have been tested in small animals and, in rare cases, in humans. Medical researchers anticipate extensive clinical applications of stem cell therapy in the future. The lack of basic knowledge concerning basic stem cell biology-survival, migration, differentiation, integration in a real time manner when transplanted into damaged CNS remains an absolute bottleneck for attempt to design stem cell therapies for CNS diseases. A major challenge to the development of clinical applied stem cell therapy in medical practice remains the lack of efficient stem cell tracking methods. As a result, the fate of the vast majority of stem cells transplanted in the human central nervous system (CNS), particularly in the detrimental effects, remains unknown. The paucity of knowledge concerning basic stem cell biology—survival, migration, differentiation, integration in real-time when transplanted into damaged CNS remains a bottleneck in the attempt to design stem cell therapies for CNS diseases. Even though excellent histological techniques remain as the gold standard, no good in vivo techniques are currently available to assess the transplanted graft for migration, differentiation, or survival. To address these issues, herein we propose strategies to investigate the lineage fate determination of derived human embryonic stem cells (hESC) transplanted in vivo into the CNS. Here, we describe a comprehensive biological Global Positioning System (bGPS) to track transplanted stem cells. But, first, we review, four currently used standard methods for tracking stem cells in vivo: magnetic resonance imaging (MRI), bioluminescence imaging (BLI), positron emission tomography (PET) imaging and fluorescence imaging (FLI) with quantum dots. We summarize these modalities and propose criteria that can be employed to rank the practical usefulness for specific applications. Based on the results of this review, we argue that additional qualities are still needed to advance these modalities toward clinical applications. We then discuss an ideal procedure for labeling and tracking stem cells in vivo, finally, we present a novel imaging system based on our experiments.

In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution

“…An appropriate in vivo imaging tool to evaluate the biology of transplanted cells in association with the therapeutic effects of gene therapy using MSCs is needed. 13 In vivo live imaging plays an important role in biomedical research. Noninvasive imaging methods, such as magnetic resonance imaging (MRI) or positron emission tomography (PET), have contributed to advances in high-resolution in vivo imaging for stem cell tracking.…”

1980-2011: Parkinson's Disease and Advance in Stem Cell Research

“…Gaining more information about the pathology of the disease, the probable behavior of the grafted cells, as well as the reciprocal interconnections between the transplants and the host environment in animal models will be useful to predict possible complications and undesirable side effects readily translatable to future clinical trials for PD patients (Li et al, 2010b). Caution needs to be adapted since xenograft models of disease in animals may not accurately predict the same response in humans due to inherent differences.…”

In vivoimaging of endogenous neural stem cells in the adult brain

“…Imaging techniques should be non-invasive, so they can be applied repetitively in the same individual in a longitudinal fashion, and thus track quantity and localization of endogenous NSC over any period of time. While considerable progress has been made in recent years to track transplanted, prelabeled cells [41][42][43][44][45][46][47] , the detection of endogenous NSCs in the living brain remains elusive. Current approaches to image eNSCs in vivo include (1) the use of transgenic animals whose eNSCs exhibit certain imaging properties; (2) labeling eNSCs in vivo by injecting a labeling substance into the brain; or (3) imaging some intrinsic and putative unique property of eNSCs with a tailored imaging assay.…”