Increased cell suspension concentration augments the survival rate of grafted tyrosine hydroxylase immunoreactive neurons

Terpstra, Brian T.; Collier, Timothy J.; Marchionini, Deanna; Levine, Nathan; Paumier, Katrina L.; Sortwell, Caryl E.

doi:10.1016/j.jneumeth.2007.06.022

Cited by 19 publications

(19 citation statements)

References 37 publications

(44 reference statements)

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“…These cells persisted and their number did not decrease further for up to 1 year after transplantation. Our cell survival rate is similar to that reported by other groups who have transplanted embryonic cells into adult rat striatum after 6-OHDA lesions (see Terpstra et al, 2007). To determine whether some of the MGE cells remained proliferative after transplantation, we labeled fixed tissue with Ki67, a marker expressed by dividing cells, and did not find Ki67 + MGE cells at any time point after the transplantation (1, 2, and 4 days, 4 weeks, 8 weeks, and 12 weeks), indicating that the MGE cells ceased dividing soon after transplantation.…”

Section: Resultssupporting

confidence: 91%

Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats

et al. 2010

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SUMMARY We investigated a strategy to ameliorate the motor symptoms of rats that received 6-hydroxydopamine (6-OHDA) lesions, a rodent model of Parkinson’s disease, through transplantation of embryonic medial ganglionic eminence (MGE) cells into the striatum. During brain development, embryonic MGE cells migrate into the striatum and neocortex where they mature into GABAergic interneurons and play a key role in establishing the balance between excitation and inhibition. Unlike most other embryonic neurons, MGE cells retain the capacity for migration and integration when transplanted into the postnatal and adult brain. We performed MGE cell transplantation into the basal ganglia of control and 6-OHDA-lesioned rats. Transplanted MGE cells survived, differentiated into GABA+ neurons, integrated into host circuitry, and modifed motor behavior in both lesioned and control rats. Our data suggest that MGE cell transplantation into the striatum is a promising approach to investigate the potential benefits of remodeling basal ganglia circuitry in neurodegenerative diseases.

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Section: Resultssupporting

confidence: 91%

Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats

et al. 2010

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“…Previous work has shown that the number of transplanted cells affects the outcome of cell therapy. When the number of transplanted cells was varied from 25,000 to 200,000 cells/ mL in a rodent model of PD, animals receiving a greater number of cells had significantly greater improvements in their functional recovery than did animals receiving a smaller graft (14). In addition, larger grafts contained more tyrosine hydroxylase immunoreactive neurons and enhanced the survival rate of the transplanted cells (14).…”

Section: Discussionmentioning

confidence: 99%

“…When the number of transplanted cells was varied from 25,000 to 200,000 cells/ mL in a rodent model of PD, animals receiving a greater number of cells had significantly greater improvements in their functional recovery than did animals receiving a smaller graft (14). In addition, larger grafts contained more tyrosine hydroxylase immunoreactive neurons and enhanced the survival rate of the transplanted cells (14). This finding was supported by a recent study demonstrating a decrease in graft volume, cell survival, and tyrosine hydroxylase immunoreactivity in transplants when a low number of cells was injected (13).…”

Section: Discussionmentioning

confidence: 99%

“…Using this method, the number of cells that are successfully transplanted can be determined, and this number has been shown, in animal models, to affect therapeutic outcome (13,14). This determination is important to standardize the transplantation technique and enhance experimental control in preclinical and clinical settings.…”

Section: Discussionmentioning

confidence: 99%

“…The number of transplanted cells has been shown to affect therapeutic outcome (13,14). The number of cells transplanted can, in theory, be determined with good accuracy using nuclear imaging methods, including SPECT and the appropriate molecular imaging probe.…”

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confidence: 99%

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99mTc-Based Imaging of Transplanted Neural Stem Cells and Progenitor Cells

Gleave

Valliant²,

Doering³

2011

Journal of Nuclear Medicine Technology

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Cell therapy for neurologic disorders will benefit significantly from progress in methods of noninvasively imaging cell transplants. The success of current cell therapy has varied, in part because of differences in cell sources, differences in transplantation procedures, and lack of understanding of cell fate after transplantation. Standardization of transplantation procedures will progress with noninvasive imaging. In turn, in vivo imaging will enhance our understanding of neural transplant biology and improve therapeutic outcomes. The goal of this study was to determine the effect of a 99m Tc-based probe on neural stem and progenitor cell transplants and validate the SPECT images of the transplanted cells. Methods: We previously developed a method to label neural stem and progenitor cells with 99m Tc to visualize these cells in the brain with SPECT. The cells were initially labeled with a permeation peptide carrying a chelate for 99m Tc. The proliferation and differentiation characteristics of the labeled cells were studied in tissue culture. In parallel experiments, the labeled cells were stereotactically injected into the rat brain, and the site of transplantation was verified with histochemistry and phosphorimaging. Results: The accuracy of the transplant location obtained by SPECT was confirmed by comparison with phosphorimages and histologic sections of the brain. The labeling did, however, decrease the proliferative capacity of the neural stem and progenitor cells. Conclusion: The labeling technique described here can be used to standardize the location of cell transplants in the brain and quantify the number of transplanted cells. However, a 99m Tc-based probe can decrease the cellular proliferation of neural progenitor cells.

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Microtransplantation of whole ganglionic eminence cells ameliorates motor deficit, enlarges the volume of grafts, and prolongs survival in a rat model of Huntington's disease

Zhu

Shu

Wang

et al. 2013

J of Neuroscience Research

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Studies have demonstrated that embryonic cell therapy is a potential approach for the treatment of Huntington's disease (HD). However, because of the limited resource of embryos, greater attention is needed in developing more efficient surgical techniques that not only enhance the therapy outcome but also avoid inefficient therapeutics of transplantation. In this study, we explored the curative effects of two different transplantation methods using a rat model of HD. Whole ganglionic eminence (WGE) cells or phosphate-buffered saline were transplanted into unilateral striatum of quinolinic acid (QA)-lesioned rats using microtransplantation instruments (with an outer diameter of 50 μm) or traditional transplantation instruments (with an outer diameter of 470 μm). Apomorphine-induced rotation test and adjusting step test were assessed after QA-induced lesion and 2, 4, 6, 8, 10, and 12 weeks after transplantation. The expression of neuronal nuclei (NeuN), dopamine, cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), and glial fibrillary acidic protein (GFAP) was analyzed at 12 weeks after transplantation. We observed that microtransplanted rats performed better in the stepping test and had higher numbers of DARPP-32-positive cells compared with traditionally transplanted rats. Moreover, microtransplantation group showed lower GFAP expression surrounding the grafts in unilateral striatum and a higher survival rate posttransplantation compared with the traditional transplantation group. We conclude that microtransplantation is capable of enhancing therapeutic efficacy in the rat model of HD. This finding establishes the basis of an alternative transplantation strategy for treatment of HD.

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Increased cell suspension concentration augments the survival rate of grafted tyrosine hydroxylase immunoreactive neurons

Cited by 19 publications

References 37 publications

Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats

Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats

99mTc-Based Imaging of Transplanted Neural Stem Cells and Progenitor Cells

Microtransplantation of whole ganglionic eminence cells ameliorates motor deficit, enlarges the volume of grafts, and prolongs survival in a rat model of Huntington's disease

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