Safety of Intrastriatal Neurotransplantation for Huntington's Disease Patients

Kopyov, Oleg; Jacques, Skip; Lieberman, Abraham; Duma, Christopher; Eagle, K. S.

doi:10.1006/exnr.1997.6685

Cited by 168 publications

(90 citation statements)

References 45 publications

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“…13,14 However, recently, Mendez et al 15,16 demonstrated that a new transplantation procedure with a multiple-graft strategy and placement of cells in both the caudate and substantia nigra of the brain benefited PD patients without the side-effects previously reported. In the case of HD, the results of transplantation of fetal striatal tissue into the striatum of HD patients showed that fetal tissue can be isolated for use in the treatment of HD and that neurological implantation of the isolated cells is safe, 9,17,18 and the transplantation of these cells may have clinical benefits with respect to motor and cognitive outcomes. 11,12,19 Despite these encouraging results, the lack of fetal tissue availability may ultimately limit the clinical utility of this treatment approach.…”

Section: Introductionmentioning

confidence: 99%

Expansion of Human Neural Precursor Cells in Large‐Scale Bioreactors for the Treatment of Neurodegenerative Disorders

Baghbaderani

Mukhida

Sen

et al. 2008

Biotechnology Progress

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The transplantation of in vitro expanded human neural precursor cells (hNPCs) represents a potential new treatment alternative for individuals suffering from incurable neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). However, in order for cell restorative therapy to have widespread therapeutic significance, it will be necessary to generate unlimited quantities of clinical grade hNPCs in a standardized method. We report here that we have developed a serum‐free medium and scale‐up protocols that allow for the generation of clinical quantities of human telencephalon‐derived hNPCs in 500‐mL computer‐controlled suspension bioreactors. The average hNPC aggregate diameter in the bioreactors was maintained below a target value of 500 μm by controlling the liquid shear field. The human cells, which were inoculated at 105 cells/mL, exhibited a doubling time of 84 h, underwent a 36‐fold expansion over the course of 18 days, and maintained an average viability of over 90%. The bioreactor‐derived hNPCs retained their nestin expression following expansion and were able to differentiate into glial and neuronal phenotypes under defined conditions. It has also been demonstrated that these hNPCs differentiated to a GABAergic phenotype that has recently been shown to be able to restore functional behavior in rat models of HD and neuropathic pain (Mukhida, K. et al. Stem Cells 2007; DOI 10.1634/stemcells.2007–0326). This study demonstrates that clinical quantities of hNPCs can be successfully and reproducibly generated under standardized conditions in computer‐controlled suspension bioreactors.

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Section: Introductionmentioning

confidence: 99%

Expansion of Human Neural Precursor Cells in Large‐Scale Bioreactors for the Treatment of Neurodegenerative Disorders

Baghbaderani

Mukhida

Sen

et al. 2008

Biotechnology Progress

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“…Several preclinical studies initially reported the efficacy of human fetal striatal tissue to provide functional recovery in a variety of rodent and nonhuman primate models of striatal neuronal loss [4][5][6][7][8][9]. On this basis, several clinical trials then assessed the potential of fetal neural transplants for the treatment of HD (Fig.…”

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confidence: 99%

“…An initial uncontrolled trial was carried out in 3 moderately advanced HD patients [4]. These patients received bilateral grafts of 8-to 10-week-old human fetal striatal primordia, each pooled from 5 to 8 donors.…”

mentioning

confidence: 99%

“…BDNF=brain-derived neurotrophic factor; Ca=caudate; LGE/MGE=lateral ganglionic eminence/medial ganglionic eminence; SVZ=subventricular zone; LV=lateral ventricle; GPe=globus externalis; GPi=globus pallidus internalis; Put=putamen; TH=Thalamus patients. Besides the lack of benefit provided by these grafts, they proved potentially unsafe; in the single patient who survived 10 years, autopsy revealed residual, donorderived fetal ependymal and periventricular cells, which were associated with multiple cysts and graft-derived mass lesions [4].…”

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confidence: 99%

“…Microdissection was performed to reduce the contaminant tissue that resulted in the development of cysts and lesions in the Kopyov clinical trial [4]. Despite the use of multiple donors and injection sites (lateral ganglionic eminence of 2 to 8 fetuses per recipient striatum, immunosuppressed for 6 months), only 8 to 10% of the recipient striata engrafted in 1 patient, who was autopsied 18 months after transplant.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

Benraiss

Goldman

2011

Neurotherapeutics

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Progenitor Cell Biology

Mehler

Kessler

1999

Arch Neurol

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A few brief years ago, damage to the central nervous system was generally perceived to be irreparable, and loss of neurons was largely viewed as an irreversible process. However, major advances in the study of neural progenitor cells have altered these perceptions, and rational approaches to the repair of the damaged nervous system using transplanted progenitor cells now seem feasible. This review will discuss the basic biology of neural progenitor cells, the mechanisms regulating the generation of neurons and glia from these cells, and the techniques that are available for preparing such cells for transplantation into the nervous system. The potential uses for these cells in treating neurologic disease will then be reviewed, and the theoretical and technical problems that may be encountered will be discussed.

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Safety of Intrastriatal Neurotransplantation for Huntington's Disease Patients

Cited by 168 publications

References 45 publications

Expansion of Human Neural Precursor Cells in Large‐Scale Bioreactors for the Treatment of Neurodegenerative Disorders

Expansion of Human Neural Precursor Cells in Large‐Scale Bioreactors for the Treatment of Neurodegenerative Disorders

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

Progenitor Cell Biology

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