Near-Infrared Fluorescence Labeling Allows Noninvasive Tracking of Bone Marrow Stromal Cells Transplanted Into Rat Infarct Brain

Sugiyama, Taku; Kuroda, Satoshi; Osanai, Toshiya; Shichinohe, Hideo; Kuge, Yuji; Ito, Masaki; Kawabori, Masahito; Iwasaki, Yoshinobu

doi:10.1227/neu.0b013e318208f891

Cited by 43 publications

(57 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an indirect approach, we evaluated the size of hemorrhage on the area of injury by measuring the endogenous NIR fluorescence of intracranial hematoma. 35 In vivo non-invasive laser scanning of CHI mice heads revealed a significant decrease in head lesion area 48 h post-administration of HUCB-derived MNCs, compared with vehicle (Fig. 5A).…”

Section: Reduction Of Brain Lesion Volume Upon Hucb-derived Cd45 + Cementioning

confidence: 93%

See 1 more Smart Citation

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Arien‐Zakay

Gincberg

Nagler³

et al. 2014

Journal of Neurotrauma

View full text Add to dashboard Cite

Treatment of traumatic brain injury (TBI) is still an unmet need. Cell therapy by human umbilical cord blood (HUCB) has shown promising results in animal models of TBI and is under evaluation in clinical trials. HUCB contains different cell populations but to date, only mesenchymal stem cells have been evaluated for therapy of TBI. Here we present the neurotherapeutic effect, as evaluated by neurological score, using a single dose of HUCB-derived mononuclear cells (MNCs) upon intravenous (IV) administration one day post-trauma in a mouse model of closed head injury (CHI). Delayed (eight days post-trauma) intracerebroventricular administration of MNCs showed improved neurobehavioral deficits thereby extending the therapeutic window for treating TBI. Further, we demonstrated for the first time that HUCBderived pan-hematopoietic CD45 positive (CD45 + ) cells, isolated by magnetic sorting and characterized by expression of CD45 and CD11b markers (96-99%), improved the neurobehavioral deficits upon IV administration, which persisted for 35 days. The therapeutic effect was in a direct correlation to a reduction in the lesion volume and decreased by pre-treatment of the cells with anti-human-CD45 antibody. At the site of brain injury, 1.5-2 h after transplantation, HUCBderived cells were identified by near infrared scanning and immunohistochemistry using anti-human-CD45 and antihuman-nuclei antibodies. Nerve growth factor and vascular endothelial growth factor levels were differentially expressed in both ipsilateral and contralateral brain hemispheres, thirty-five days after CHI, measured by enzyme-linked immunosorbent assay. These findings indicate the neurotherapeutic potential of HUCB-derived CD45+ cell population in a mouse model of TBI and propose their use in the clinical setting of human TBI.

show abstract

Section: Reduction Of Brain Lesion Volume Upon Hucb-derived Cd45 + Cementioning

confidence: 93%

“…These conditions enabled evaluation of hemorrhage on the injury area by measuring the endogenous NIR fluorescence of intracranial hematoma. 35 Histological approach. Twenty one days post-trauma, mice were deeply anesthetized and perfusion fixed with instilled 4% paraformaldehyde in PBS.…”

Section: Measurements Of Brain Lesion Area and Volumementioning

confidence: 99%

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Arien‐Zakay

Gincberg

Nagler³

et al. 2014

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…The BMSCs were isolated under sterile conditions from male 8-wk-old transgenic rats expressing enhanced green fluorescent protein (GFP) (Japan SLC Inc.) and were cultured as previously reported (14,18,22,23). The cells were passed 3 times for subsequent experiments.…”

Section: Bmsc Preparationmentioning

confidence: 99%

“…Permanent MCA occlusion was induced, as described previously (14,18,22,23). Briefly, anesthesia was induced by 4.0% isoflurane in N 2 O/O 2 (70:30) and was maintained with 2.0% isoflurane in N 2 O/O 2 (70:30).…”

Section: Permanent Middle Cerebral Artery (Mca) Occlusion Modelmentioning

confidence: 99%

“…These techniques would enable validation of the therapeutic benefits of BMSC transplantation without any bias. Other recent studies have suggested that MRI and optical imaging might provide useful information on the engraftment of BMSCs in the host CNS (14)(15)(16)(17)(18). However, there are few studies that indicate the utility of an imaging technique to monitor the response of the host CNS after cell therapy (19)(20)(21).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Bone Marrow Stromal Cell Transplantation Enhances Recovery of Local Glucose Metabolism After Cerebral Infarction in Rats: A Serial ¹⁸F-FDG PET Study

et al. 2012

Self Cite

View full text Add to dashboard Cite

This study aimed to assess whether 18 F-FDG PET could serially monitor the beneficial effects of bone marrow stromal cells (BMSC) on cerebral glucose metabolism when transplanted into the infarct brain of rats. Methods: The BMSC from green fluorescent protein transgenic rats or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 d after permanent middle cerebral artery occlusion of rats. Local glucose metabolism was semiquantitatively measured at 6 and 35 d after ischemia using 18 F-FDG PET. Motor function was serially evaluated throughout the experiments. At 35 d after ischemia, immunohistochemistry was performed to evaluate the phenotype of BMSC and their effects on the expression of brain-type glucose transporters. Results: BMSC transplantation not only enhanced functional recovery but also promoted the recovery of glucose utilization in the periinfarct area when stereotactically transplanted at 1 wk after ischemia. The engrafted cells were widely distributed, and most expressed a neuron-specific protein, NeuN. BMSC transplantation also prevented the pathologic upregulation of glucose transporters in the periinfarct neocortex. Conclusion: The present findings strongly suggest that the BMSC may enhance functional recovery by promoting the recovery of local glucose metabolism in the periinfarct area when directly transplanted into the infarct brain at clinically relevant timing. The BMSC also inhibit the pathologic upregulation of brain-isoform glucose transporters type 1 and 3. 18 F-FDG PET may be a valuable modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situations.

show abstract

The potential role of bone marrow mesenchymal stromal cells in the treatment of ischemic stroke

Pan

Sun

2016

The Biology and Therapeutic Application of Mesenchymal Cells

View full text Add to dashboard Cite

Near-Infrared Fluorescence Labeling Allows Noninvasive Tracking of Bone Marrow Stromal Cells Transplanted Into Rat Infarct Brain

Abstract: NIR fluorescence imaging is valuable in monitoring the behaviors of donor cells in the rodent brain. The results would allow new opportunities to develop noninvasive NIR fluorescence imaging as a modality to track the BMSCs transplanted into the brain.

Cited by 43 publications

References 46 publications

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Bone Marrow Stromal Cell Transplantation Enhances Recovery of Local Glucose Metabolism After Cerebral Infarction in Rats: A Serial ¹⁸F-FDG PET Study

The potential role of bone marrow mesenchymal stromal cells in the treatment of ischemic stroke

Contact Info

Product

Resources

About

Near-Infrared Fluorescence Labeling Allows Noninvasive Tracking of Bone Marrow Stromal Cells Transplanted Into Rat Infarct Brain

Abstract: NIR fluorescence imaging is valuable in monitoring the behaviors of donor cells in the rodent brain. The results would allow new opportunities to develop noninvasive NIR fluorescence imaging as a modality to track the BMSCs transplanted into the brain.

Cited by 43 publications

References 46 publications

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

Bone Marrow Stromal Cell Transplantation Enhances Recovery of Local Glucose Metabolism After Cerebral Infarction in Rats: A Serial 18F-FDG PET Study

The potential role of bone marrow mesenchymal stromal cells in the treatment of ischemic stroke

Contact Info

Product

Resources

About

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Bone Marrow Stromal Cell Transplantation Enhances Recovery of Local Glucose Metabolism After Cerebral Infarction in Rats: A Serial ¹⁸F-FDG PET Study