Transplantation of Clonal Neural Precursor Cells Derived from Adult Human Brain Establishes Functional Peripheral Myelin in the Rat Spinal Cord

Akiyama, Yukinori; Honmou, Osamu; Kato, Takaaki; Uede, T; Hashi, Kazuo; Kocsis, Jeffery D.

doi:10.1006/exnr.2000.7539

Cited by 231 publications

(138 citation statements)

References 55 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…Several lines of evidence indicate that the remyelination was from the transplanted bone marrow cells and not from endogenous host cells. Our studies were carried out within 3 weeks after EB-X lesion induction, which is well within the time at which persistent demyelination is confirmed in a large number of control studies (Blakemore and Crang, 1985;Franklin et al, 1996;Honmou et al, 1996;Kato et al, 2000;Akiyama et al, 2001Akiyama et al, , 2002aSasaki et al, 2001). However, the possible facilitation of recruitment of cells outside of the lesion zone from the injection procedure cannot be completely ruled out.…”

Section: Discussionmentioning

confidence: 69%

“…It is well established that stem cells from one region will, when placed to ectopic CNS sites, differentiate with a terminal phenotype appropriate for that ectopic site (Gage et al, 1995;Lundberg and Bjorklund, 1996;Hammang et al, 1997;Snyder et al, 1997;Brustle et al, 1999;Akiyama et al, 2001). The extra-cellular environment into which transplanted stem cells has an important influence on their fate in vivo (Lundberg and Bjorklund, 1996;Hammang et al, 1997;Snyder et al, 1997;Brustle et al, 1999;Akiyama et al, 2001). Pathological CNS tissue is a different environment than intact CNS tissue and markedly alters the terminal differentiated phenotype of transplanted cells (Gage et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord

Inoue

Honmou

Oka

et al. 2003

Glia

Self Cite

102

View full text Add to dashboard Cite

The remyelinating potential of autologous bone marrow cells was studied after direct injection and following intravenous injection into rats with a demyelinated lesion in the spinal cord. Both focal and intravenous injections of acutely isolated mononuclear bone marrow cell fractions resulted in varying degrees of remyelination. Suspensions of bone marrow cells collected from the same rat were delivered at varied concentrations (10 2 to 10 5 for direct injection and 10 4 to 10 7 for i.v. injections). The lesions were examined histologically 3 weeks after transplantation. Light microscopic examination revealed remyelination in the dorsal funiculus with both injection protocols, but the extent of remyelination was proportional to the number of injected cells. To attain the same relative density of remyelination achieved by direct injection, intravenous administration of cells required delivery of substantially more cells (two orders of magnitude). However, the availability of autologous bone marrow cells in large number and the potential for systemically delivering cells to target lesion areas without neurosurgical intervention suggest the potential utility of intravenous cell delivery as a prospective therapeutic approach in demyelinating disease.

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord

Inoue

Honmou

Oka

et al. 2003

Glia

Self Cite

102

View full text Add to dashboard Cite

show abstract

“…Many of the myelinated axons in Figure 3D surround a central cell body and nucleus that is reminiscent of oligodendrocyte myelination. In this regard, cell transplantation studies using neural precursor cells derived from brain and directly injected into demyelinative lesions report that both central and peripheral myelin can form from the transplanted cells (Keirstead et al, 1999;Akiyama et al, 2001). …”

Section: Resultsmentioning

confidence: 99%

Remyelination of the spinal cord following intravenous delivery of bone marrow cells

Akiyama

Radtke

Honmou

et al. 2002

Glia

Self Cite

303

164

View full text Add to dashboard Cite

Bone marrow contains a population of pluripotent cells that can differentiate into a variety of cell lineages, including neural cells. When injected directly into the demyelinated spinal cord they can elicit remyelination. Recent work has shown that following systemic delivery of bone marrow cells functional improvement occurs in contusive spinal cord injury and stroke models in rat. We report here that secondary to intravenous introduction of an acutely isolated bone marrow cell fraction (mononuclear fraction) from adult rat femoral bones separated on a density gradient, ultrastructurally defined remyelination occurs throughout a focal demyelinated spinal cord lesion. The anatomical pattern of remyelination was characteristic of both oligodendrocyte and Schwann cell myelination; conduction velocity improved in the remyelinated axons. When the injected bone marrow cells were transfected to express LacZ, β-galactosidase reaction product was observed in some myelin-forming cells in the spinal cord. Intravenous injection of other myelin-forming cells (Schwann cells and olfactory ensheathing cells) or the residual cell fraction of the gradient did not result in remyelination, suggesting that remyelination was specific to the delivery of the mononuclear fraction. While the precise mechanism of the repair, myelination by the bone marrow cells or facilitation of an endogenous repair process, cannot be fully determined, the results demonstrate an unprecedented level of myelin repair by systemic delivery of the mononuclear cells.

show abstract

“…Indeed, such PSA-NCAM+ glial precursors, growing as neurospheres and also termed as oligospheres [135,138], efficiently myelinated the brains of shi mice [138][139][140], remyelinated 95 to 100% of axons following local injection into the dorsal columns of rats [141], and efficiently migrated along inflamed white matter tracts of rats with EAE [94,95]. Similarly, adult human SVZ precursors remyelinated the adult rat spinal cord [142]. Finally, multipotential NSC also showed a capacity to perform efficient myelination in the spinal cords of shiverer mouse, md rat, and sh pup [143][144][145], as well as in adult animals with traumatic spinal cord injury [146,147].…”

Section: Cell Replacementmentioning

confidence: 99%

Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

View full text Add to dashboard Cite

The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

show abstract

Transplantation of Clonal Neural Precursor Cells Derived from Adult Human Brain Establishes Functional Peripheral Myelin in the Rat Spinal Cord

Cited by 231 publications

References 55 publications

Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord

Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord

Remyelination of the spinal cord following intravenous delivery of bone marrow cells

Cell Therapy for Multiple Sclerosis

Contact Info

Product

Resources

About