A novel cell transplantation protocol and its application to an ALS mouse model

Morita, Eri; Watanabe, Yauhiro; Ishimoto, Miho; Nakano, Tetsuo; Kitayama, Michio; Yasui, Kenichi; Fukada, Yasuyo; Doi, Keiko; Karunaratne, Asanka; Murrell, Wayne; Sutharsan, Ratneswary; Mackay‐Sim, Alan; Hata, Yutaka; Nakashima, Kenichiro

doi:10.1016/j.expneurol.2008.07.011

Cited by 68 publications

(42 citation statements)

References 32 publications

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“…Interestingly, female mice responded slightly better to the cell treatment, as observed in other studies in transgenic mutant hSOD1 mice [130,131]. Characterization of the graft 6 weeks post-transplantation revealed that the cells were positive for the early neural marker nestin and rarely expressed the glial marker GFAP.…”

Section: Knippenberg Et Al Showed That Intraspinal Transplantation Osupporting

confidence: 74%

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

Izrael¹,

Guy²,

Itskovitz‐Eldor³

et al. 2018

Astrocyte - Physiology and Pathology

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Astrocytes are the major cell population in the central nervous system (CNS) and play pivotal role in CNS homeostasis and functionality. Malfunction of astrocytes were implicated in multiple neurodegenerative diseases and disorders, including amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), brain stroke, Parkinson's disease (PD), and Alzheimer disease (AD). These new insights led to the rationale that transplantation of healthy and functional human astrocytes could support survival of neurons and be of therapeutic value in treating neurodegenerative diseases. Here, we will mainly focus on the role of astrocytes in ALS disease, the major cell sources for generation of human astrocytes, or astrocyte like cells and show how multiple preclinical studies demonstrate the efficacy of these cells in animal models. In addition, we will cover immerging early stage clinical trials that are currently being conducted using human astrocytes or human astrocyte like cell population.

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Section: Knippenberg Et Al Showed That Intraspinal Transplantation Osupporting

confidence: 74%

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

Izrael¹,

Guy²,

Itskovitz‐Eldor³

et al. 2018

Astrocyte - Physiology and Pathology

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“…Data obtained using various injury models support the view that OEC transplants can reduce cavitation, increase axonal sprouting and regeneration, and a moderate degree of functional motoric recovery (Li et al, 1997;Ramon-Cueto et al, 2000;Collazos-Castro et al, 2005;Lopez-Vales et al, 2007;Sasaki et al, 2007). Moreover, transplanted OECs promote neuroplasticity in murine models of stroke (Shyu et al, 2008), restore functional deficits in rat model of Parkinson's disease (Agrawal et al, 2004), and OECs have been transplanted to an amyotrophic lateral sclerosis (ALS) mouse model (Morita et al, 2008). In clinic, Lima et al (2006) and Feron et al (2005) used adult autologous olfactory mucosa OECs from patients to repair spinal cord injury.…”

mentioning

confidence: 68%

The Immunohistochemical Characterization of Human Fetal Olfactory Bulb and Olfactory Ensheathing Cells in Culture as a Source for Clinical CNS Restoration

Liu²,

Wang³

et al. 2010

The Anatomical Record

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Clinical studies have expanded the therapeutic olfactory ensheathing cells (OECs) transplantation to different human Central Nervous System (CNS) diseases. In fact, the OEC transplantation in clinic is a mixture of olfactory bulb cells; they even have not demonstrated that they have such a subpopulation yet. However, as a source of OECs transplantation, the development and identification of human fetal OECs are still need more understanding, because some surgery try to restoration CNS injury with a more purity of OEC cultures generated by a number of different procedures. In this article, twelve human fetal olfactory bulb (OB) samples were obtained from six fetuses in 20 weeks of gestation, it was studied by immunofluorescence on histological sections and cultured cells with multiple antibodies under confocal microscopy. The P75NTR positive OB-OECs (olfactory ensheathing cell from the olfactory bulb) were present in both outer olfactory nerve layers and glomerular layer. The percentage of OB cells in culture, about 22.31 was P75NTR positive, 45.77 was S100b, and 31.92 was GFAP. P75NTR and GFAP were coexpressed with S100b, respectively; however, P75NTR was not coexpressed with GFAP in human fetal OECs. It is suggested that the localization and development of human OECs in OB are different to those in rodent, and the P75NTR immunohistological staining is still necessary to identify and characterize human fetal OECs in culture before transplantation. Anat Rec, 293:359-369, 2010. V V C 2009 Wiley-Liss, Inc.

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“…The intrathecal application improves the transplant of MSC in some neurodegenerative diseases (Habisch et al 2007;Morita et al 2008), because the application avoids some brain damage produced by a needle or cannula, which is known to induce expression of stem cell factors (Sun et al 2004). In addition, the intrathecal injection of bone marrow stromal cells shows some therapeutic benefit without any marked adverse effect in clinical trial (Saito et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

et al. 2011

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Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin (DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma. However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain.

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A novel cell transplantation protocol and its application to an ALS mouse model

Cited by 68 publications

References 32 publications

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

The Immunohistochemical Characterization of Human Fetal Olfactory Bulb and Olfactory Ensheathing Cells in Culture as a Source for Clinical CNS Restoration

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

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