Obliteration of a Posttraumatic Spinal Cord Cyst with Solid Human Embryonic Spinal Cord Grafts: First Clinical Attempt

Falci, Scott; Holtz, Anders; Åkesson, Elisabet; Azizi, Mohammad; Ertzgaard, Per; Hultling, Claes; Kjældgaard, A.; Level, R.; Ringdén, Olle; Westgren, Magnus; Lammertse, Daniel P.; Seiger, Åke

doi:10.1089/neu.1997.14.875

Cited by 90 publications

(35 citation statements)

References 19 publications

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“…46 At a later stage following injury investigations have been directed to reducing gliosis and collagenous fibrosis which are believed by some to obstruct regeneration mechanically. 47,48 In recent times, regeneration research has taken a new direction in finding human application with much attention being now given to exploring multipotential stem cells in bringing about CNS repair and regeneration.…”

Section: The Autonomic Motor Systemmentioning

confidence: 99%

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: The Autonomic Motor Systemmentioning

confidence: 99%

Neuropathology: the foundation for new treatments in spinal cord injury

2004

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“…38 Other techniques involve the transplantation of embryonic tissues or Schwann cells. 68,69 Falci et al 70 have gone one step further by introducing human foetal spinal cord tissue into the post-traumatic cysts in the human SCI patient. However, they state that the intention is not to obtain regeneration but to prevent the development of post-traumatic syringomyelia for which some success has been achieved.…”

Section: The Continuing Lesionmentioning

confidence: 99%

The applied neuropathology of human spinal cord injury

Kakulas

1999

Spinal Cord

109

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“…Grafts of embryonic brain and spinal cord tissue have been reported to survive in the spinal cord [46][47][48][49][50][51] of experimental animals and considerable experimental data from animal studies indicate that transplanted fetal spinal cord tissue improves recovery from SCI. 52,53 Fetal spinal cord tissue has previously been transplanted into patients with chronic SCI and symptomatic syringomyelia without reports of adverse events [54][55][56] and there is only one definitive report of tumor growth following CNS transplantation of fetal tissue in a patient. 57 While OEGs are very interesting cells with therapeutic potential, many important steps that normally are considered the essential groundwork of a clinical trial have not been completed for fetal OB-derived cell transplantation.…”

Section: Discussionmentioning

confidence: 99%

Rapid recovery of segmental neurological function in a tetraplegic patient following transplantation of fetal olfactory bulb-derived cells

2005

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Study design: Case report. Objective: Report rapid neurological changes in a complete tetraplegic following a cell injection procedure. Setting: Beijing, China. Methods: ASIA/IMSOP neurological scale. Immunostaining of cell cultures. Cellular transplantation to effect functional restoration following spinal cord injury (SCI) has been hypothesized to cause improvements through axonal regeneration, increased plasticity, or axonal remyelination. Several human trials are in preliminary phases. We report a rapid improvement in motor and sensory functions in the segment adjacent to the level of complete SCI within days following cellular transplantation of cultured fetal olfactory bulb-derived cells. The patient was an 18-year-old C3 ASIA A complete tetraplegic 18 months post-injury who had been neurologically stable for more than 6 months. Results: Within 48 h of cell transplantation, the patient improved one ASIA motor grade in the left elbow flexors and began to show right wrist extensor function. Descent of the sensory level occurred within 4 days and then the rate of change slowed. He is now a C5 motor and C4 sensory complete tetraplegic. Cellular cultures prepared in the same facility showed viable human cells that labeled for nestin and GFAP. Conclusion: We hypothesize that improved transmission in intact fibers subserving the zone of partial preservation accounts for these early improvements. We emphasize the need for further independent analysis of the outcomes of this and other preliminary cell transplant studies.

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Obliteration of a Posttraumatic Spinal Cord Cyst with Solid Human Embryonic Spinal Cord Grafts: First Clinical Attempt

Cited by 90 publications

References 19 publications

Neuropathology: the foundation for new treatments in spinal cord injury

Neuropathology: the foundation for new treatments in spinal cord injury

The applied neuropathology of human spinal cord injury

Rapid recovery of segmental neurological function in a tetraplegic patient following transplantation of fetal olfactory bulb-derived cells

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