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Book: Glial precursor cell transplantation therapy for neurotrauma and multiple sclerosis

Kulbatski, Iris

(Progress in histochemistry and cytochemistry ; 43,3)

2008

Author's details	Iris Kulbatski
Series title	Progress in histochemistry and cytochemistry ; 43,3
Collection
Language	English
Size	S. 124 - 176
Publisher	Elsevier
Publishing place	Amsterdam u.a.
Publishing country	Netherlands
Document type	Book
HBZ-ID	HT015664266
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Stem/precursor cell-based CNS therapy: the importance of circumventing immune suppression by transplanting autologous cells.

Kulbatski, Iris

Stem cell reviews and reports

2010 Volume 6, Issue 3, Page(s) 405–410

Abstract: Stem/precursor cell (SPC) therapy for neurodegeneration and neurotrauma has enormous therapeutic potential, but despite ongoing research efforts the success of clinical trials remains limited. Therapies that utilize immune suppression in combination with ...

Abstract	Stem/precursor cell (SPC) therapy for neurodegeneration and neurotrauma has enormous therapeutic potential, but despite ongoing research efforts the success of clinical trials remains limited. Therapies that utilize immune suppression in combination with SPC transplantation have thus far failed to consider the beneficial role of the immune system in central nervous system (CNS) recovery. Systemic immune suppression may prevent neural repair, and in some cases exacerbate the underlying disorder. Until about a decade ago, immunosuppression for CNS disorders was viewed as a therapeutic target, based on the perception that all immune activity in the CNS was destructive. However, recent studies show that the infiltration of blood-borne immune cells into the CNS following neurotrauma and during chronic neurodegeneration promote CNS protection and regeneration. In the context of SPC therapies, although immune suppression prevents rejection of non-autologous cell grafts, it also prevents the restorative immune response by eliminating the immune mediated guidance cues that are required for SPCs to migrate to the location they are needed, and preventing SPC-mediated immunomodulation. This article argues in favor of transplanting autologous SPCs, particularly bone marrow derived cells. The therapeutic use of autologous SPCs for neural repair circumvents the need for concomitant immune suppression, exploits the immunomodulatory capacity of these cells, and maintains the immune niche that supports neural repair and is required to guide these cells to their appropriate locations. Overall, such an approach accommodates the requirements for translational therapeutics, and provides a standardized platform for reconciling the inherent controversies in the science.
MeSH term(s)	Animals ; Central Nervous System Diseases/immunology ; Central Nervous System Diseases/therapy ; Humans ; Immunosuppression/adverse effects ; Models, Biological ; Stem Cell Transplantation/methods ; Transplantation Immunology/physiology ; Transplantation, Autologous
Language	English
Publishing date	2010-03-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-010-9141-6
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Article ; Online: Emerging Applications for Optically Enabled Intravital Microscopic Imaging in Radiobiology.

Maeda, Azusa / Kulbatski, Iris / DaCosta, Ralph S

Molecular imaging

2015 Volume 14, Issue 9, Page(s) 7290201500022

Abstract: Radiation therapy is an effective cancer treatment used in over 50% of cancer patients. Preclinical research in radiobiology plays a major role in influencing the translation of radiotherapy-based treatment strategies into clinical practice. Studies have ...

Abstract	Radiation therapy is an effective cancer treatment used in over 50% of cancer patients. Preclinical research in radiobiology plays a major role in influencing the translation of radiotherapy-based treatment strategies into clinical practice. Studies have demonstrated that various components of tumors and their microenvironments, including vasculature, immune and stem cells, and stromal cells, can influence the response of solid tumors to radiation. Optically enabled imaging techniques used in experimental animal models of cancer offer a unique and powerful way to quantitatively track spatiotemporal changes in these tumor components in vivo at macro-, meso-, and microscopic resolutions following radiotherapy. In this review, we discuss the role of both well-established and emerging intravital microscopy techniques for studying tumors and their microenvironment in vivo, in response to irradiation. The development and application of new animal models, small animal microirradiation technologies, and multimodal optically enabled intravital microscopy techniques are emphasized within the framework of preclinical radiobiology research. We also comment on the potential influence that these newer imaging techniques may have on the clinical translation of new preclinical radiobiology discoveries.
Language	English
Publishing date	2015-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2137435-1
ISSN	1536-0121 ; 1535-3508
ISSN (online)	1536-0121
ISSN	1535-3508
DOI	10.2310/7290.2015.00022
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Article ; Online: Emerging Applications for Optically Enabled Intravital Microscopic Imaging in Radiobiology.

Maeda, Azusa / Kulbatski, Iris / DaCosta, Ralph S

Molecular imaging

2015 Volume 14, Page(s) 452–474

Abstract	Radiation therapy is an effective cancer treatment used in over 50% of cancer patients. Preclinical research in radiobiology plays a major role in influencing the translation of radiotherapy-based treatment strategies into clinical practice. Studies have demonstrated that various components of tumors and their microenvironments, including vasculature, immune and stem cells, and stromal cells, can influence the response of solid tumors to radiation. Optically enabled imaging techniques used in experimental animal models of cancer offer a unique and powerful way to quantitatively track spatiotemporal changes in these tumor components in vivo at macro-, meso-, and microscopic resolutions following radiotherapy. In this review, we discuss the role of both well-established and emerging intravital microscopy techniques for studying tumors and their microenvironment in vivo, in response to irradiation. The development and application of new animal models, small animal microirradiation technologies, and multimodal optically enabled intravital microscopy techniques are emphasized within the framework of preclinical radiobiology research. We also comment on the potential influence that these newer imaging techniques may have on the clinical translation of new preclinical radiobiology discoveries.
MeSH term(s)	Animals ; Humans ; Immunomodulation ; Intravital Microscopy/methods ; Models, Animal ; Neoplasms/diagnostic imaging ; Optical Imaging/methods ; Radiobiology ; Radionuclide Imaging
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2137435-1
ISSN	1536-0121 ; 1535-3508
ISSN (online)	1536-0121
ISSN	1535-3508
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Article: Region-specific differentiation potential of adult rat spinal cord neural stem/precursors and their plasticity in response to in vitro manipulation.

Kulbatski, Iris / Tator, Charles H

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

2009 Volume 57, Issue 5, Page(s) 405–423

Abstract: This study characterized the differentiation of neural stem/precursor cells (NSPCs) isolated from different levels of the spinal cord (cervical vs lumbar cord) and different regions along the neuraxis (brain vs cervical spinal cord) of adult male Wistar ... ...

Abstract	This study characterized the differentiation of neural stem/precursor cells (NSPCs) isolated from different levels of the spinal cord (cervical vs lumbar cord) and different regions along the neuraxis (brain vs cervical spinal cord) of adult male Wistar enhanced green fluorescent protein rats. The differentiation of cervical spinal cord NSPCs was further examined after variation of time in culture, addition of growth factors, and changes in cell matrix and serum concentration. Brain NSPCs did not differ from cervical cord NSPCs in the percentages of neurons, astrocytes, or oligodendrocytes but produced 26.9% less radial glia. Lumbar cord NSPCs produced 30.8% fewer radial glia and 6.9% more neurons compared with cervical cord NSPCs. Spinal cord NSPC differentiation was amenable to manipulation by growth factors and changes in in vitro conditions. This is the first study to directly compare the effect of growth factors, culturing time, serum concentration, and cell matrix on rat spinal cord NSPCs isolated, propagated, and differentiated under identical conditions.
MeSH term(s)	Animals ; Astrocytes/cytology ; Brain/cytology ; Cell Differentiation ; Cells, Cultured ; Ciliary Neurotrophic Factor/pharmacology ; Culture Media ; Green Fluorescent Proteins/genetics ; Male ; Neuroglia/cytology ; Neurons/cytology ; Oligodendroglia/cytology ; Platelet-Derived Growth Factor/pharmacology ; Rats ; Rats, Transgenic ; Spinal Cord/anatomy & histology ; Spinal Cord/cytology ; Stem Cells/cytology ; Time Factors
Chemical Substances	Ciliary Neurotrophic Factor ; Culture Media ; Platelet-Derived Growth Factor ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2009-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218208-7
ISSN	1551-5044 ; 0022-1554
ISSN (online)	1551-5044
ISSN	0022-1554
DOI	10.1369/jhc.2008.951814
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Article ; Online: Potential of magnetic resonance-guided focused ultrasound for intracranial hemorrhage: an in vitro feasibility study.

Harnof, Sagi / Hananel, Arik / Zilby, Zion / Kulbatski, Iris / Hadani, Moshe / Kassell, Neal

International journal of stroke : official journal of the International Stroke Society

2014 Volume 9, Issue 1, Page(s) 40–47

Abstract: Background: Intracranial hemorrhage has a mortality rate of up to 40-60% due to the lack of effective treatment. Magnetic resonance-guided focused ultrasound may offer a breakthrough noninvasive technology, by allowing accurate delivery of focused ... ...

Abstract	Background: Intracranial hemorrhage has a mortality rate of up to 40-60% due to the lack of effective treatment. Magnetic resonance-guided focused ultrasound may offer a breakthrough noninvasive technology, by allowing accurate delivery of focused ultrasound, under the guidance of real-time magnetic resonance imaging. Aim: The purpose of the current study was to optimize the acoustic parameters of magnetic resonance-guided focused ultrasound for effective clot liquefaction, in order to evaluate the feasibility of magnetic resonance-guided focused ultrasound for thrombolysis. Methods: Body (1·1 MHz) and brain (220 kHz) magnetic resonance-guided focused ultrasound systems (InSightec Ltd, Tirat Carmel, Israel) were used to treat tube-like (4 cc), round (10 cc), and bulk (300 cc) porcine blood clots in vitro, using burst sonications of one-second to five-seconds, a duty cycle of 5-50%, and peak acoustic powers between 600 and 1200 W. Liquefied volumes were measured as hyperintense regions on T2-weighted magnetic resonance images for body unit sonications (duration of one-second, duty cycle of 10%, and power of 500-1200 W). Liquefaction efficiency was calculated for brain unit sonications (duration of one-second, duty cycle of 10%, power of 600 W, and burst length between 0·1 ms and 100 ms). Results: Liquified lesion volume increased as power was raised, without a thermal rise. For brain unit sonications, a power setting of 600 W and ultrashort sonications (burst length between 0·1 and 1·0 ms) resulted in liquefaction efficacy above 50%, while longer burst duration yielded lower efficacy. Conclusions: These results demonstrate the feasibility of obtaining reproducible, rapid, efficient, and accurate blood clot lysis using the magnetic resonance-guided focused ultrasound system. Further in vivo studies are needed to validate the feasibility of magnetic resonance-guided focused ultrasound as a treatment modality for intracranial hemorrhage.
MeSH term(s)	Animals ; Feasibility Studies ; Intracranial Hemorrhages/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Mechanical Thrombolysis/methods ; Surgery, Computer-Assisted/methods ; Swine ; Ultrasonography
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2303728-3
ISSN	1747-4949 ; 1747-4930
ISSN (online)	1747-4949
ISSN	1747-4930
DOI	10.1111/ijs.12051
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Article: Transplantation of adult rat spinal cord stem/progenitor cells for spinal cord injury.

Parr, Ann M / Kulbatski, Iris / Tator, Charles H

Journal of neurotrauma

2007 Volume 24, Issue 5, Page(s) 835–845

Abstract: Stem/progenitor cells derived from the ependymal region of the spinal cord have the ability to self-renew and are multipotential for neurons and glia. These cells may have the ability to regenerate the injured mammalian spinal cord as they do in some ... ...

Abstract	Stem/progenitor cells derived from the ependymal region of the spinal cord have the ability to self-renew and are multipotential for neurons and glia. These cells may have the ability to regenerate the injured mammalian spinal cord as they do in some lower vertebrates. However, the optimal conditions for transplantation and the fate of transplanted cells are not fully known. In the current study, spinal cord stem/progenitor cells were cultured from adult male rats expressing enhanced green fluorescent protein (eGFP). Neurospheres were transplanted at the time of clip compression injury (35-g force) into the injury site, or 1 mm rostral and caudal to the injury site. Neurospheres were also transplanted into a subacute model (day 9 after injury) and a chronic model (day 28 after injury). Functional recovery was also studied in an acute injury model with weekly locomotor testing over a 16-week period. A significant increase in cell survival at 7 days was seen in rats receiving rostral and caudal injections as compared to injection directly into the site of injury. A significant increase in cell survival was also seen in rats receiving subacute transplants at 9 days after injury. Transplanted cells differentiated primarily into astrocytes (31.2%) and oligodendrocytes (50.3%), and a small number of neurons (1%). No improvement was seen in the Basso, Beattie and Bresnahan (BBB) locomotor rating scale after acute transplantation as compared with injury only, although surviving transplanted cells were identified that had migrated across the injury site from the rostral and caudal injection sites.
MeSH term(s)	Adult Stem Cells/physiology ; Animals ; Biomarkers/metabolism ; Cell Differentiation/physiology ; Cell Movement/physiology ; Cell Proliferation ; Cell Survival/physiology ; Cells, Cultured ; Disease Models, Animal ; Female ; Graft Survival/physiology ; Green Fluorescent Proteins ; Male ; Motor Activity/physiology ; Nerve Regeneration/physiology ; Neuroglia/physiology ; Neurons/physiology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Recovery of Function/physiology ; Spheroids, Cellular/physiology ; Spheroids, Cellular/transplantation ; Spinal Cord Injuries/physiopathology ; Spinal Cord Injuries/therapy ; Stem Cell Transplantation/methods ; Treatment Outcome
Chemical Substances	Biomarkers ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2007-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2006.3771
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Article ; Online: Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies.

Wu, Yichao Charlie / Kulbatski, Iris / Medeiros, Philip J / Maeda, Azusa / Bu, Jiachuan / Xu, Lizhen / Chen, Yonghong / DaCosta, Ralph S

Journal of biomedical optics

2014 Volume 19, Issue 8, Page(s) 85002

Abstract: Bacterial infection significantly impedes wound healing. Clinical diagnosis of wound infections is subjective and suboptimal, in part because bacteria are invisible to the naked eye during clinical examination. Moreover, bacterial infection can be ... ...

Abstract	Bacterial infection significantly impedes wound healing. Clinical diagnosis of wound infections is subjective and suboptimal, in part because bacteria are invisible to the naked eye during clinical examination. Moreover, bacterial infection can be present in asymptomatic patients, leading to missed opportunities for diagnosis and treatment. We developed a prototype handheld autofluorescence (AF) imaging device (Portable Real-time Optical Detection, Identification and Guidance for Intervention - PRODIGI) to noninvasively visualize and measure bacterial load in wounds in real time. We conducted preclinical pilot studies in an established nude mouse skin wound model inoculated with bioluminescent Staphylococcus aureus bacteria. We tested the feasibility of longitudinal AF imaging for in vivo visualization of bacterial load in skin wounds, validated by bioluminescence imaging. We showed that bacteria (S. aureus), occult to standard examination, can be visualized in wounds using PRODIGI. We also detected quantitative changes in wound bacterial load over time based on the antibiotic treatment and the correlation of bacterial AF intensity with bacterial load. AF imaging of wounds offers a safe, noninvasive method for visualizing the presence, location, and extent of bacteria as well as measuring relative changes in bacterial load in wounds in real time.
MeSH term(s)	Animals ; Bacterial Load/instrumentation ; Cell Tracking/instrumentation ; Computer Systems ; Equipment Design ; Equipment Failure Analysis ; Feasibility Studies ; Mice ; Optical Imaging/instrumentation ; Reproducibility of Results ; Sensitivity and Specificity ; Staphylococcal Skin Infections/microbiology ; Staphylococcal Skin Infections/pathology ; Wound Infection/microbiology ; Wound Infection/pathology
Language	English
Publishing date	2014-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1309154-2
ISSN	1560-2281 ; 1083-3668
ISSN (online)	1560-2281
ISSN	1083-3668
DOI	10.1117/1.JBO.19.8.085002
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Article ; Online: Potential of magnetic resonance-guided focused ultrasound for intracranial hemorrhage: an in vivo feasibility study.

Harnof, Sagi / Zibly, Zion / Hananel, Arik / Monteith, Stephen / Grinfeld, Javier / Schiff, Gilat / Kulbatski, Iris / Kassell, Neal

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2014 Volume 23, Issue 6, Page(s) 1585–1591

Abstract: Background: Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative ... ...

Abstract	Background: Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept. Methods: The transcranial effectiveness of MRgFUS was tested ex vivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900 W for 5-10 seconds. A 3-mL clot was also introduced in a porcine brain and sonicated in vivo with one 5-second pulse of 700 W through a bone window or with 3000 W when treated through an ex vivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images. Results: In both in vivo porcine blood clot through a craniectomy model and the porcine clot in an ex vivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue. Conclusions: Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an in vivo porcine model of ICH and in 2 ex vivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.
MeSH term(s)	Animals ; Feasibility Studies ; Humans ; Intracranial Hemorrhages/therapy ; Magnetic Resonance Imaging/methods ; Models, Anatomic ; Swine ; Ultrasonic Therapy/instrumentation
Language	English
Publishing date	2014-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2013.12.044
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Article: Calcium entry through L-type calcium channels is essential for neurite regeneration in cultured sympathetic neurons.

Kulbatski, Iris / Cook, Douglas J / Tator, Charles H

Journal of neurotrauma

2004 Volume 21, Issue 3, Page(s) 357–374

Abstract: Previous work showed that a post-neuritotomy rise in [Ca2+]i is required for regeneration. We tested the following hypotheses in cultured sympathetic neurons: (1) blocking L-type channels at the time of injury inhibits regeneration; (2) enhancing Ca2+ ... ...

Abstract	Previous work showed that a post-neuritotomy rise in [Ca2+]i is required for regeneration. We tested the following hypotheses in cultured sympathetic neurons: (1) blocking L-type channels at the time of injury inhibits regeneration; (2) enhancing Ca2+ entry through L-type Ca2+ channels enhances regeneration; (3) L-type Ca2+ channel distribution is predominantly on the soma and proximal neurites of uninjured and injured neurons. To visualize L-type Ca2+ channels and block Ca2+ influx, the fluorescent dihydropyridine antagonist, DM-BODIPY, was used. Our results show that regeneration is markedly inhibited by the antagonist when administered 20 min. prior to injury, in the presence or absence of nerve growth factor (NGF) (p < 0.0001). Severe degeneration of proximal and distal neurites was seen 48 h after injury. Regeneration was minimally inhibited by the antagonist when administered 5 min after injury (p < 0.05), but not inhibited when administered 2 or 24 h after injury (p > 0.05). We found that L-type channels are distributed ubiquitously on the soma and neurites of uninjured and injured cells, and on regenerating neurites. The addition of the L-type channel agonist, BayK8644, (1 microM) 20 min prior to injury enhanced neurite length at 24 h post-injury (p = 0.002). Blocking L-type channels did not affect the viability of uninjured or injured cells. For the first time, it has been shown that Ca2+ entry through L-type Ca2+ channels is essential for post-neuritotomy sympathetic neurite regeneration, and that this effect shows a strict temporal dependency. We also demonstrated that regeneration can be enhanced by increasing Ca2+ influx through L-type channels.
MeSH term(s)	Animals ; Animals, Newborn ; Boron Compounds/pharmacology ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/physiology ; Calcium Signaling/physiology ; Cell Culture Techniques ; Ganglia, Spinal/injuries ; Ganglia, Spinal/physiopathology ; Nerve Regeneration/drug effects ; Nerve Regeneration/physiology ; Neurites/physiology ; Pyridines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Superior Cervical Ganglion/injuries ; Superior Cervical Ganglion/physiopathology
Chemical Substances	Boron Compounds ; Calcium Channel Blockers ; Calcium Channels, L-Type ; Pyridines ; dihydropyridine-BODIPY
Language	English
Publishing date	2004-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/089771504322972130
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