Tracking Neural Stem Cells in Patients with Brain Trauma

Zhu, Jiaan; Zhou, Liangfu; XingWu, FengGe

doi:10.1056/nejmc055304

Cited by 273 publications

(214 citation statements)

References 5 publications

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“…In previous studies, we used SPIOs to label adult human NSCs and tracked their migration in host human brains following transplantation (Zhu et al, 2006). In this study, we labeled iPSCs-derived NSCs with SPIOs and then imaged labeled cell distribution in host animal brains and spinal cords in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Then single cells were labeled with Feridex and green fluorescent protein (GFP) (Zhu et al, 2006). After incubation with SPIOs overnight, the Prussian Blue (PB) method was used for the detection of iron within cell plasma.…”

Section: Preparation Of Spio-labeled Nscsmentioning

confidence: 99%

“…Previously, we reported the first clinical study about tracking migration of NSCs labeled with superparamagnetic iron oxides (SPIO) by magnetic resonance imaging (MRI) for brain trauma patients (Zhu et al, 2006). To address the problems above and assess the viability of iPSCs transplants for CNS injury, we tried to track the distribution of iPSCsderived NSCs noninvasively in traumatic brain injury (TBI) rats and spinal cord injury (SCI) monkeys in vivo in this study.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tracking Induced Pluripotent Stem Cells–Derived Neural Stem Cells in the Central Nervous System of Rats and Monkeys

Sha

Sun

et al. 2013

Cellular Reprogramming

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Despite of the immense breakthroughs of induced pluripotent stem cells (iPSCs), clinical application of iPSCs and their derivates remains hampered by a lack of definitive in vivo studies. Here, we attempted to track iPSCsderived neural stem cells (NSCs) in the rodent and primate central nervous system (CNS) and explore their therapeutic viability for stem cell replacement in traumatic brain injury (TBI) rats and monkeys with spinal cord injury (SCI). Superparamagnetic iron oxide (SPIO) particles were used to label iPSCs-derived NSCs in vitro. Labeled NSCs were implanted into TBI rats and SCI monkeys 1 week after injury, and then imaged using gradient reflection echo (GRE) sequence by 3.0T magnetic resonance imaging (MRI) scanner. MRI analysis was performed at 1, 7, 14, 21, and 30 days, respectively, following cell transplantation. Pronounced hypointense signals were initially detected at the cell injection sites in rats and monkeys and were later found to extend progressively to the lesion regions, demonstrating that iPSCs-derived NSCs could migrate to the lesion area from the primary sites. The therapeutic efficacy of iPSCs-derived NSCs was examined concomitantly through functional recovery tests of the animals. In this study, we tracked iPSCs-derived NSCs migration in the CNS of TBI rats and SCI monkeys in vivo for the first time. Functional recovery tests showed obvious motor function improvement in transplanted animals. These data provide the necessary foundation for future clinical application of iPSCs for CNS injury.

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Spio-labeled Nscsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tracking Induced Pluripotent Stem Cells–Derived Neural Stem Cells in the Central Nervous System of Rats and Monkeys

Sha

Sun

et al. 2013

Cellular Reprogramming

Self Cite

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“…Importantly, we have used a noninvasive multimodality imaging approach to monitor autologous iPSC transplantation in a large animal model of cardiac delivery. Both the PET reporter gene and the MR iron oxide labeling techniques we employed allow for accurate localization of cells and are directly applicable to human patients (30). Furthermore, we have generated functional endothelial cells from ciPSCs and demonstrated the therapeutic potential of these cells in murine models of hindlimb ischemia and myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells

Lee

Plews

et al. 2011

Journal of Biological Chemistry

110

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Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia.

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“…With informed consent, such experimental intervention is allowed in paragraph 35 of the Declaration of Helsinki (DoH, 2008), and practiced in many countries in the world. Numerous such interventions have been carried out in China, with some having been reported in medical journals (Gu et al, 2003;Zhu, 2006) and shown repeatedly on state television (see for example, CCTV, 2007CCTV, , 2010. Such patient-driven forms of experimental treatments are commonly provided by doctors in first-tier hospitals, and are not usually linked to commercial interests.…”

Section: Patient-versus Profit-driven Experimental Interventions Withmentioning

confidence: 99%

Medical innovation and national experimental pluralism: Insights from clinical stem cell research and applications in China

Rosemann

2013

BioSocieties

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The article focuses on the integration process of clinical stem cell research in China in the international arena of high-profile science. This development is analyzed against the background of a well-established landscape of informal and frequently for-profit forms of clinical experimentation with stem cells. In doing so, I trace the institutionalization of experimental clinical stem cell research and applications in China, its stepwise problematization, and metamorphosis into an object of regulatory concern and intervention. It will become clear that the transition toward adoption of an internationally recognized standard system in the clinical stem cell field is a complex and highly contested process. The long-standing absence of a coherent statecentered regulatory approach for clinical stem cell research and applications in China, has not only given rise to the realization of new economic opportunities, but also to a multi-stranded innovation culture, which is characterized by knowledge exchanges and collaborations between highly diverging socio-technical and epistemic communities. I will make sense of these processes through the concept of "national experimental pluralism".

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Tracking Neural Stem Cells in Patients with Brain Trauma

Cited by 273 publications

References 5 publications

Tracking Induced Pluripotent Stem Cells–Derived Neural Stem Cells in the Central Nervous System of Rats and Monkeys

Tracking Induced Pluripotent Stem Cells–Derived Neural Stem Cells in the Central Nervous System of Rats and Monkeys

Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells

Medical innovation and national experimental pluralism: Insights from clinical stem cell research and applications in China

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