Global gene and cell replacement strategies via stem cells

Park, Kook In; Ourednik, Jitka; Ourednik, Václav; Taylor, R. M.; Aboody, Karen S.; Auguste, Kurtis I.; Lachyankar, Mahesh B.; Redmond, D. Eugene; Snyder, Evan Y.

doi:10.1038/sj.gt.3301721

Cited by 142 publications

(86 citation statements)

References 67 publications

(83 reference statements)

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“…For instance, NSC introduced into newborn 'meander tail' mice, which are deficient in cerebellar granule cells are able to migrate into the neuron-deficient sites and replace a proportion of the lost cells. 56,57 Another neurological mutant is the 'reeler' mouse which shows aberrant neuronal migration during development. NSC implanted at birth have been shown to improve the cytoarchitecture of the developing cerebral cortex.…”

Section: Stem Cell Experiments On Animal Models Of Neurological Diseasementioning

confidence: 99%

“…This change occurred presumably by the NSC replacing the extracellular matrix signal normally provided by the gene 'reelin' which is mutated in the 'reeler mouse'. 56 A further model of neurological disease is the 'shiverer' mouse, which lacks myelin basic protein (MBP). In experiments, NSC were shown to posses the ability to migrate widely in these mice.…”

Section: Stem Cell Experiments On Animal Models Of Neurological Diseasementioning

confidence: 99%

“…The treatment corrects the defect morphologically but unfortunately no functional improvement is evident from these experiments. 56 NSC have been used in other animal models of human neurological disorders with variable outcomes. Examples are multiple sclerosis, Parkinson's disease and motor neuron disease (ALS).…”

Section: Stem Cell Experiments On Animal Models Of Neurological Diseasementioning

confidence: 99%

“…In animal experiments, it has been shown that introduced stem cells may not grow into neurons and axons but in some way provide an environment which causes the host tissue to recover from degenerations. 56 Putting these important considerations aside how would ESC bring about a cure? An analysis of requirements to reach this objective follows.…”

Section: The Futurementioning

confidence: 99%

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Neuropathology: the foundation for new treatments in spinal cord injury

2004

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The first step essential in the search for a cure of human spinal cord injury (SCI) is to appreciate the complexity of the disorder. In this regard, it is not only the loss of ambulation but the sensory and autonomic changes that are equally important in recovery. In addition, there are the serious social emotional psychological and lifestyle effects of SCI which should also be taken into account. It is also true that no two SCI lesions are alike as each is the result of a SCI unique to that individual. Clinically of utmost importance is the segmental level of injury and whether it is complete, incomplete or discomplete (loss of all neurological functions below the injury but with physiological or anatomical continuity of Central nervous system tracts across the lesion). We are not concerned here with primary and secondary prevention or methods designed to limit the severity of the lesion after the event, important as they are, but with the requirements for a cure. Clearly, the greater the number of nerve fibers that can be preserved in the acute stage, the better will be the end result. Our focus at present is on the end-stage lesion with the aim of showing that a cure for SCI will depend upon establishing functionally useful central axonal regeneration and reestablishing physiological reconnections. Existing experimental methods are based on stimulating axonal regeneration by neutralizing inhibitory factors, adding positive trophisms and creating a permissive environment. Better results are obtained by bridging the gap with grafts of peripheral nerves or transplants of Schwann cells and genetically engineered fibroblasts. Recently, the potential for stem cells to enhance this process has created great interest. This is because of the ability of pluripotential cells to differentiate into neural tissue. A cure based on the physiopathology of SCI requires pyramidal, extrapyramidal, sensory, cerebellar and autonomic pathways to be regenerated with their appropriate neurotransmitters restored and reflexes integrated physiologically and in synchrony. In human SCI, there is a very long distance anatomically for axonal regrowth to occur in order to reach their relevant nuclei. This is because of continuing Wallerian degeneration. It also presumes that the target neurons are intact and that there has been no transneuronal degeneration above or below the lesion. Alternatively, in place of regenerated long axons, a multisynaptic pathway may be constructed from stem cells that have developed into neurons. Whether such a pathway would restore useful neurological functions is unknown. At present, the transplant and grafting research teams are exploring these possibilities in experimental animals. Moderate success in gaining axonal regeneration has been reported; however, it must be appreciated that the human lesion differs considerably from that of the experimental animal. In order to be successful, the neuropathology and neurophysiology of human SCI must be taken into account. The purpose of this review is to place the req...

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Section: Stem Cell Experiments On Animal Models Of Neurological Diseasementioning

confidence: 99%

Section: Stem Cell Experiments On Animal Models Of Neurological Diseasementioning

confidence: 99%

Section: Stem Cell Experiments On Animal Models Of Neurological Diseasementioning

confidence: 99%

Section: The Futurementioning

confidence: 99%

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Neuropathology: the foundation for new treatments in spinal cord injury

2004

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“…Most of the transplantation experience acquired the last two decades was focused on fetal neuronal grafts (Isacson, 2003;Lindvall et al, 2004;Richardson et al, 2004). The objective was to replace degenerated neurons in pathologies, such as Parkinson's and Huntington's disease, characterized by degeneration restricted to a limited brain area (Bjorklund and Lindvall, 2000;Brazel and Rao, 2004;Freed et al, 2001;Palfi et al, 1998;Park et al, 2002;Redmond et al, 2001). However, despite the great enthusiasm generated by this approach, ethical controversies, immune rejection, and lack of fetal donors remain a major problem.…”

Section: Introductionmentioning

confidence: 99%

Primate adult brain cell autotransplantation, a new tool for brain repair?

Brunet

Rouiller

Wannier

et al. 2005

Experimental Neurology

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If successful, autologous brain cell transplantation is an attractive approach to repair lesions and restore function of the central nervous system. We demonstrate that monkey adult brain cells obtained from cortical biopsy and kept in culture for 4 weeks exhibit neural progenitor characteristics. After reimplantation into a lesion area of the donor cerebral cortex, these cells can successfully survive and acquire neuronal characteristics over time. These results open new perspectives in the field of brain repair and may lead to future clinical applications.

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Stem Cells

Sylvester

Longaker²

2004

Arch Surg

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egenerative medicine and emerging biotechnologies stand to revolutionize the practice of medicine. Advancements in stem cell biology, including embryonic and postnatal somatic stem cells, have made the prospect of tissue regeneration a potential clinical reality. Short of reproductive cloning, these same technologies, properly used, could allow for the creation of replacement tissue for the deficient host. To provide a concise review for surgeons on the current science and biology of stem cells, we surveyed the scientific literature, MEDLINE, and relevant political headlines that illuminate the stem cell discussion; the issues are summarized in this review. Building on this conceptual framework, the related issues of clinical promise and the political debate enveloping this emerging technology are examined. A basic understanding of stem cell biology is paramount to stay informed of this emerging technology and the national debate.

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Global gene and cell replacement strategies via stem cells

Abstract: The inherent biology of neural stem cells (NSCs

Cited by 142 publications

References 67 publications

Neuropathology: the foundation for new treatments in spinal cord injury

Neuropathology: the foundation for new treatments in spinal cord injury

Primate adult brain cell autotransplantation, a new tool for brain repair?

Stem Cells

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