Effects of prolonged delivery of brain-derived neurotrophic factor on the fate of neural stem cells transplanted into the developing rat retina

Suzuki, Takuya; Ooto, Sotaro; Akagi, Tadamichi; Amemiya, Kaori; Igarashi, Rie; Mizushima, Yutaka; Takahashi, Masayo

doi:10.1016/j.bbrc.2003.08.076

Cited by 22 publications

(21 citation statements)

References 23 publications

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“…However, GFP-expressing BM-MSCs cells which showed morphological differentiation did not co-express with MAP2ab and GFAP. In immunostaining patterns of MAP2ab, only the cell cytoplasm was clearly stained, while cell nucleus and dendrites were lightly stained [10, 34, 54, 55]. …”

Section: Resultsmentioning

confidence: 99%

Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells into the Developing Mouse Eye

Lee

Jang

et al. 2011

Acta Histochem. Cytochem

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Mesenchymal stem cells (MSCs) have been studied widely for their potential to differentiate into various lineage cells including neural cells in vitro and in vivo. To investigate the influence of the developing host environment on the integration and morphological and molecular differentiation of MSCs, human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transplanted into the developing mouse retina. Enhanced green fluorescent protein (GFP)-expressing BM-MSCs were transplanted by intraocular injections into mice, ranging in ages from 1 day postnatal (PN) to 10 days PN. The survival dates ranged from 7 days post-transplantation (DPT) to 28DPT, at which time an immunohistochemical analysis was performed on the eyes. The transplanted BM-MSCs survived and showed morphological differentiation into neural cells and some processes within the host retina. Some transplanted cells expressed microtubule associated protein 2 (MAP2ab, marker for mature neural cells) or glial fibrillary acid protein (GFAP, marker for glial cells) at 5PN 7DPT. In addition, some transplanted cells integrated into the developing retina. The morphological and molecular differentiation and integration within the 5PN 7DPT eye was greater than those of other-aged host eye. The present findings suggest that the age of the host environment can strongly influence the differentiation and integration of BM-MSCs.

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Section: Resultsmentioning

confidence: 99%

Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells into the Developing Mouse Eye

Lee

Jang

et al. 2011

Acta Histochem. Cytochem

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“…The number of spontaneously regenerating neurons is so low that up to now the possibility of a regeneration of brain infarcts has been excluded. However, it is conceivable that functionally relevant neurogenesis is promoted by trophic factors, such as brain derived neurotrophic factor (BDNF) or other growth factors (Dempsey et al, 2003;Suzuki et al, 2003). Regeneration therapy has also been attempted by transplantation of immortalised neuroepithelial cells (Modo et al, 2002), neural stem cells (Chu et al, 2004) and stem cells derived from fetal brain tissue (Borlongan et al, 1997), bone marrow (Grabowski et al, 1995;Chen et al, 2003) or umbilical cord blood (Willing et al, 2003).…”

Section: Regenerationmentioning

confidence: 99%

Pathophysiology and Therapy of Experimental Stroke

2006

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1. Stroke is the neurological evidence of a critical reduction of cerebral blood flow in a circumscribed part of the brain, resulting from the sudden or gradually progressing obstruction of a large brain artery. Treatment of stroke requires the solid understanding of stroke pathophysiology and involves a broad range of hemodynamic and molecular interventions. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research. 2. The first chapter deals with the hemodynamics of focal ischemia with particular emphasis on the collateral circulation of the brain, the regulation of blood flow and the microcirculation. In the second chapter the penumbra concept of ischemia is discussed, providing a detailed list of the physiological, biochemical and structural viability thresholds of ischemia and examples of how these thresholds can be applied for imaging the penumbra. The third chapter summarizes the pathophysiology of infarct progression, focusing on the role of peri-infarct depolarisation, the multitude of putative molecular injury pathways, brain edema and inflammation. Finally, the fourth chapter provides an overview of currently discussed therapeutic approaches, notably the effect of mechanical or thrombolytic reperfusion, arteriogenesis, pharmacological neuroprotection, ischemic preconditioning and regeneration. 3. The main emphasis of the review is placed on the balanced differentiation between hemodynamic and molecular factors contributing to the manifestation of ischemic injury in order to provide a rational basis for future therapeutic interventions.

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“…In a recent study, NSCs transplanted along with solutions of slow-releasing BDNF into the vitreous cavity of developing rats resulted in the majority of donor cells integrating into the host retina, but the difference was not statistically signifi cant compared with the control group. These data indicated that the neuroprotective effect of BDNF's slow-releasing system on NSCs was limited as well [25] . To this end, we planned to utilize gene transfer to ensure continuous and prolonged delivery of neurotrophic factors by the donor cells.…”

Section: Wwwchinapharcom Zhou Xm Et Almentioning

confidence: 90%

A rat model for studying neural stem cell transplantation

et al. 2009

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Aim: The goal of this project was to develop a rat model for neural stem cell (NSC) transplantation studies in which NSCs were modifi ed with brain-derived neurotrophic factor (BDNF) genes that may permit extensive and reliable analysis of the transplants. Methods: NSCs were cultured and purifi ed by limiting dilution assay in vitro and infected with recombinant retrovirus pLXSN-BDNF (BDNF-NSCs) and retrovirus pLXSN (p-NSCs). The expression of BDNF genes in transgenic and control NSC groups was measured by FQ-PCR and ELISA assays. NSCs were then transplanted into the subretinal space of normal rat retinas in four groups, which included NSCs alone, BDNF-NSCs, phosphate buffered saline (PBS) control, and normal control. Survival, migration, and differentiation of donor cells in host retinas were observed with optical coherence tomography (OCT), Heidelberg retina angiograph (HRA), and immunohistochemistry, respectively. Results: The results obtained by FQ-PCR demonstrated that the copy numbers of BDNF gene templates from BDNF-NSCs were the highest among the four groups (P<0.05). Consistent with the results of FQ-PCR, BDNF protein level from the supernatant of the BDNFNSCs group was much higher than that of the other two groups (P<0.05) as suggested by the ELISA assays. HRA and OCT showed that graft cells could successfully survive. Immunohistochemical analysis revealed that transplanted BDNF-NSCs could migrate in the host retinas and differentiate into glial cells and neurons three months after transplantation. Conclusion: BDNF promotes NSCs to migrate and differentiate into neural cells in the normal host retinas.

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Effects of prolonged delivery of brain-derived neurotrophic factor on the fate of neural stem cells transplanted into the developing rat retina

Cited by 22 publications

References 23 publications

Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells into the Developing Mouse Eye

Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells into the Developing Mouse Eye

Pathophysiology and Therapy of Experimental Stroke

A rat model for studying neural stem cell transplantation

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