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5. Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury

Author

Bedi, Supinder S., Aertker, Benjamin M., Liao, George P., Caplan, Henry W., Bhattarai, Deepa, Mandy, Fanni, Mandy, Franciska, Fernandez, Luis G., Zelnick, Pamela, Mitchell, Matthew B., Schiffer, Walter, Johnson, Margaret, Denson, Emma, Prabhakara, Karthik, Xue, Hasen, Smith, Philippa, Uray, Karen, Olson, Scott D., Mays, Robert W., and Cox, Jr, Charles S.

Published
2018
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11. Systemic multipotent adult progenitor cells protect the cerebellum after asphyxia in fetal sheep

Author

MS Neonatologie, Brain, Child Health, Gussenhoven, Ruth, Ophelders, Daan R.M.G., Dudink, Jeroen, Pieterman, Kay, Lammens, Martin, Mays, Robert W., Zimmermann, Luc J., Kramer, Boris W., Wolfs, Tim G.A.M., Jellema, Reint K., MS Neonatologie, Brain, Child Health, Gussenhoven, Ruth, Ophelders, Daan R.M.G., Dudink, Jeroen, Pieterman, Kay, Lammens, Martin, Mays, Robert W., Zimmermann, Luc J., Kramer, Boris W., Wolfs, Tim G.A.M., and Jellema, Reint K.

Published
2021

16. Distinguishing roles of the membrane-cytoskeleton and cadherin mediated cell-cell adhesion in generating different Na+, K+-ATPase distributions in polarized epithelia

Author

Marrs, James A., Napolitano, Eugene W., Murphy-Erdosh, Cynthia, Mays, Robert W., Reichardt, Louis F., and Nelson, W. James

Subjects
Cell adhesion -- Research, Adenosine triphosphatase -- Analysis, Cells -- Composition, Proteins -- Analysis, Biological sciences
Abstract

Membrane-cytoskeleton and cadherins have distinct functions in producing various distributions of sodium, potassium-adenosine triphosphatase (Na+, KT-ATPase) in polarized epithelia. Na+, K+-ATPase is apically situated, while B-cadherin is in the lateral part. Both of them, along with the membrane-cytoskeletal proteins, ankyrin and fodrin, exist in muti-protein complexes.

Published
1993

17. Delivery of Na+,K+-ATPase in polarized epithelial cells

Author

Gottardi, Cara J., Caplan, Michael J., Siemers, Kathleen A., Duncan, Alice, Mays, Robert W., Ryan, Timothy A., Wollner, Debra A., Nelson, W. James, Zurzolo, Chiara, and Rodriguez-Boulan, Enrique

Subjects
Adenosine triphosphatase -- Physiological aspects, Membrane proteins -- Physiological aspects, Epithelial cells -- Physiological aspects, Enzyme kinetics -- Physiological aspects, Science and technology, Physiological aspects
Abstract

The sodium and potassium ion-stimulated adenosine triphosphatase ([Nat.sup.+], [K.sup+] -ATPase) is an essential membrane protein found in all vertebrate cells that maintains ionic gradients, electrical potential, and osmotic balance [1]. [...]

Published
1993

18. Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population

Author

Walker Peter A, Bedi Supinder S, Shah Shinil K, Jimenez Fernando, Xue Hasen, Hamilton Jason A, Smith Philippa, Thomas Chelsea P, Mays Robert W, Pati Shibani, and Cox Charles S

Subjects
Multipotent adult progenitor cells, Traumatic brain injury, Stem cells, Splenocytes, Blood brain barrier, Microglia, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Introduction We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population. Methods C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4+/CD25+/FOXP3+ T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86+ M1 and CD206+ M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPC:splenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation. Results Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPC:splenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis. Conclusions The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC-mediated neuroprotection.

Published
2012
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19. Multipotent Adult Progenitor Cells, but Not Tissue Inhibitor of Matrix Metalloproteinase-3, Increase Tissue Sparing and Reduce Urological Complications following Spinal Cord Injury

Author

Jones, James M., primary, DePaul, Marc A., additional, Gregory, Cynthia R., additional, Lang, Bradley T., additional, Xie, Hua, additional, Zhu, Meihua, additional, Rutten, Michael J., additional, Mays, Robert W., additional, Busch, Sarah A., additional, Pati, Shibani, additional, and Gregory, Kenton W., additional

Published
2019
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20. Systemic multipotent adult progenitor cells improve long-term neurodevelopmental outcomes after preterm hypoxic-ischemic encephalopathy

Author

Barkhuizen, Melinda, primary, van Mechelen, Ralph, additional, Vermeer, Marijne, additional, Chedraui, Peter, additional, Paes, Dean, additional, van den Hove, Daniel L.A., additional, Vaes, Bart, additional, Mays, Robert W., additional, Steinbusch, Harry W.M., additional, Robertson, Nicola J., additional, Kramer, Boris W., additional, and Gavilanes, Antonio W.D., additional

Published
2019
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22. Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells

Author

Donders, Raf, primary, Bogie, Jeroen F.J., additional, Ravanidis, Stylianos, additional, Gervois, Pascal, additional, Vanheusden, Marjan, additional, Marée, Raphaël, additional, Schrynemackers, Marie, additional, Smeets, Hubert J.M., additional, Pinxteren, Jef, additional, Gijbels, Kristel, additional, Walbers, Sara, additional, Mays, Robert W., additional, Deans, Robert, additional, Van Den Bosch, Ludo, additional, Stinissen, Piet, additional, Lambrichts, Ivo, additional, Gyselaers, Wilfried, additional, and Hellings, Niels, additional

Published
2018
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23. Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Hess, David C, primary, Wechsler, Lawrence R, additional, Clark, Wayne M, additional, Savitz, Sean I, additional, Ford, Gary A, additional, Chiu, David, additional, Yavagal, Dileep R, additional, Uchino, Ken, additional, Liebeskind, David S, additional, Auchus, Alexander P, additional, Sen, Souvik, additional, Sila, Cathy A, additional, Vest, Jeffrey D, additional, and Mays, Robert W, additional

Published
2017
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26. Recent progress in translational research on neurovascular and neurodegenerative disorders

Author

Demuth, Hans-Ulrich, Dijkhuizen, Rick M, Otte, Willem M, Petzold, Gabor C, Plesnila, Nikolaus, Reiser, Georg, Reymann, Klaus G, Rueger, Maria A, Saur, Dorothee, Savitz, Sean I, Schilling, Stephan, Spratt, Neil J, Farr, Tracy D, Turner, Renée J, Vemuganti, Raghu, Vivien, Denis, Yepes, Manuel, Zille, Marietta, Boltze, Johannes, contributors, ISN&N meeting, Bauer, Adam Q, Giffard, Rona G, Gounis, Matthew J, Gelderblom, Mathias, Gröger, Victoria, Henrich-Noack, Petra, Von Hörsten, Stephan, Howells, David D, Kempski, Oliver, Kim, Yun-Hee, Lambertsen, Kate L, Lee, Jin-Moo, Leonard, Anna, Liesz, Arthur, Horsburgh, Karen, Macrae, I Mhairi, Mays, Robert W, Mcleod, Damian D, Neumann, Jens, Nudo, Randolph J, Offner, Halina, Rossner, Steffen, Selim, Magdy, Sohrabji, Farida, Yin, Kejie, Iadecola, Costantino, Walter, Jochen, Ziemann, Ulf, Michalski, Dominik, Murphy, Tim H, Orbe, Josune, and Publica

Subjects
sex differences, 0301 basic medicine, diagnosis [Cerebrovascular Disorders], therapy [Cerebrovascular Disorders], cerebral ischemia, Translational Research, Biomedical, 0302 clinical medicine, Translational Medical Research, Stroke, cerebral small vessel disease, Cerebrovascular Disorders/diagnosis, Late stage, Neurodegenerative Diseases, Alzheimer's disease, stroke, Neurology, neuroprotection, in vivo imaging, hemorrhage, Alzheimer’s disease, Research Article, therapy [Neurodegenerative Diseases], brain, diagnosis [Neurodegenerative Diseases], Translational research, Neurodegenerative Diseases/diagnosis, neuroimmunology, Neuroprotection, 03 medical and health sciences, dementia, translational research, vascular cognitive impairment, neurorepair, experimental therapy, Developmental Neuroscience, medicine, Journal Article, Animals, Humans, Dementia, ddc:610, business.industry, medicine.disease, Neurovascular bundle, Demenz, Mechanical thrombectomy, Cerebrovascular Disorders, 030104 developmental biology, Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery, Dementia research, RC
Abstract

The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundamental progress in evidence-based medicine to improve the patient’s outcome. This has been paralleled by a swift increase in our understanding of pathomechanisms underlying many neurovascular diseases and most prevalent forms of dementia. Taken together, these current advances offer the potential to overcome almost two decades of marginally successful translational research on stroke and dementia, thereby spurring the entire field of translational neuroscience. Moreover, they may also pave the way for the renaissance of classical neuroprotective paradigms.\ud \ud This review reports and summarizes some of the most interesting and promising recent achievements in neurovascular and dementia research. It highlights sessions from the 9th International Symposium on Neuroprotection and Neurorepair that have been discussed from April 19th to 22nd in Leipzig, Germany. To acknowledge the emerging culture of interdisciplinary collaboration and research, special emphasis is given on translational stories ranging from fundamental research on neurode- and -regeneration to late stage translational or early stage clinical investigations.

Published
2017

27. Multipotent adult progenitor cells for hypoxic-ischemic injury in the preterm brain

Author

Jellema, Reint K., Ophelders, Daan R.M.G., Zwanenburg, Alex, Nikiforou, Maria, Delhaas, Tammo, Andriessen, Peter, Mays, Robert W., Deans, Robert, Germeraad, Wilfred T.V., Wolfs, Tim G.A.M., Kramer, Boris W., Jellema, Reint K., Ophelders, Daan R.M.G., Zwanenburg, Alex, Nikiforou, Maria, Delhaas, Tammo, Andriessen, Peter, Mays, Robert W., Deans, Robert, Germeraad, Wilfred T.V., Wolfs, Tim G.A.M., and Kramer, Boris W.

Abstract

Background: Preterm infants are at risk for hypoxic-ischemic encephalopathy. No therapy exists to treat this brain injury and subsequent long-term sequelae. We have previously shown in a well-established pre-clinical model of global hypoxia-ischemia (HI) that mesenchymal stem cells are a promising candidate for the treatment of hypoxic-ischemic brain injury. In the current study, we investigated the neuroprotective capacity of multipotent adult progenitor cells (MAPC®), which are adherent bone marrow-derived cells of an earlier developmental stage than mesenchymal stem cells and exhibiting more potent anti-inflammatory and regenerative properties. Methods: Instrumented preterm sheep fetuses were subjected to global hypoxia-ischemia by 25 min of umbilical cord occlusion at a gestational age of 106 (term ~147) days. During a 7-day reperfusion period, vital parameters (e.g., blood pressure and heart rate; baroreceptor reflex) and (amplitude-integrated) electroencephalogram were recorded. At the end of the experiment, the preterm brain was studied by histology. Results: Systemic administration of MAPC therapy reduced the number and duration of seizures and prevented decrease in baroreflex sensitivity after global HI. In addition, MAPC cells prevented HI-induced microglial proliferation in the preterm brain. These anti-inflammatory effects were associated with MAPC-induced prevention of hypomyelination after global HI. Besides attenuation of the cerebral inflammatory response, our findings showed that MAPC cells modulated the peripheral splenic inflammatory response, which has been implicated in the etiology of hypoxic-ischemic injury in the preterm brain. Conclusions: In a pre-clinical animal model MAPC cell therapy improved the functional and structural outcome of the preterm brain after global HI. Future studies should establish the mechanism and long-term therapeutic effects of neuroprotection established by MAPC cells in the developing preterm brain ex

Published
2015

29. Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

Author

DePaul, Marc A., primary, Palmer, Marc, additional, Lang, Bradley T., additional, Cutrone, Rochelle, additional, Tran, Amanda P., additional, Madalena, Kathryn M., additional, Bogaerts, Annelies, additional, Hamilton, Jason A., additional, Deans, Robert J., additional, Mays, Robert W., additional, Busch, Sarah A., additional, and Silver, Jerry, additional

Published
2015
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30. Neuroinflammatory signals enhance the immunomodulatory and neuroprotective properties of multipotent adult progenitor cells

Author

Ravanidis, Stylianos, primary, Bogie, Jeroen F. J., additional, Donders, Raf, additional, Craeye, David, additional, Mays, Robert W., additional, Deans, Robert, additional, Gijbels, Kristel, additional, Bronckaers, Annelies, additional, Stinissen, Piet, additional, Pinxteren, Jef, additional, and Hellings, Niels, additional

Published
2015
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31. Stem cell therapies as an emerging paradigm in stroke (STEPS)

Author

Wechsler, Lawrence, Steindler, Dennis, Borlongan, Cesar, Chopp, Michael, Savitz, Sean, Deans, Robert, Caplan, Louis, Hess, David, Mays, Robert W., Boltze, Johannes, and Publica

Subjects
Schlaganfall, Zelltherapie, Stammzelle, analeptische Therapie
Abstract

Investigators developing cellular therapy for stroke face many challenges. Preclinical models used for cellular therapy studies should be relevant to human stroke and predictive of benefit despite differences in stroke size, cerebrovascular anatomy, immune status, and neurological responses. Translating preclinical testing to human trials is compounded by consideration of delivery method and translation of dosing with cell survival. Many issues must be approached in designing clinical trials of cellular therapy for stroke, including appropriate outcome measures, controlling for confounding factors such as rehabilitation therapy, and possible surrogate outcomes using imaging such as MRI and newer imaging techniques. It is also important to establish standardized clinical protocols and clinical database registries in advance of early proof-of-concept studies. Investigators must adopt a standardized nomenclature and characterization schema for cell products to accurately define potency and determine clinical outcome from early proof-of-concept studies. The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to bring together clinical and basic researchers with industry and regulatory representatives to assess the critical issues in the field and to create a framework to guide future investigations.

Published
2009

32. 3-Indolyl sultams as selective CRTh2 antagonists

Author

Tumey, L. Nathan, Robarge, Michael J., Gleason, Elizabeth, Song, Jianping, Murphy, Steven M., Ekema, George, Doucette, Chris, Hanniford, Doug, Palmer, Marc, Pawlowski, Gary, Danzig, Joel, Loftus, Margaret, Hunady, Karen, Sherf, Bruce, Mays, Robert W., Stricker-Krongrad, Alain, Brunden, Kurt R., Bennani, Youssef L., and Harrington, John J.

Published
2010
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33. Intravenous Multipotent Adult Progenitor Cell Therapy Attenuates Activated Microglial/Macrophage Response and Improves Spatial Learning After Traumatic Brain Injury

Author

Bedi, Supinder S., primary, Hetz, Robert, additional, Thomas, Chelsea, additional, Smith, Philippa, additional, Olsen, Alex B., additional, Williams, Stephen, additional, Xue, Hasen, additional, Aroom, Kevin, additional, Uray, Karen, additional, Hamilton, Jason, additional, Mays, Robert W., additional, and Cox, Charles S., additional

Published
2013
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41. Behavioral and Histological Characterization of Intrahippocampal Grafts of Human Bone Marrow-Derived Multipotent Progenitor Cells in Neonatal Rats with Hypoxic-Ischemic Injury

Author

Yasuhara, Takao, primary, Matsukawa, Noriyuki, additional, Yu, Guolong, additional, Xu, Lin, additional, Mays, Robert W., additional, Kovach, Jim, additional, Deans, Robert J., additional, Hess, David C., additional, Carroll, James E., additional, and Borlongan, Cesar V., additional

Published
2006
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43. Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists

Author

Robarge, Michael J., primary, Bom, David C., additional, Nathan Tumey, L., additional, Varga, Norbert, additional, Gleason, Elizabeth, additional, Silver, Daniel, additional, Song, Jianping, additional, Murphy, Steven M., additional, Ekema, George, additional, Doucette, Chris, additional, Hanniford, Doug, additional, Palmer, Marc, additional, Pawlowski, Gary, additional, Danzig, Joel, additional, Loftus, Margaret, additional, Hunady, Karen, additional, Sherf, Bruce A., additional, Mays, Robert W., additional, Stricker-Krongrad, Alain, additional, Brunden, Kurt R., additional, Harrington, John J., additional, and Bennani, Youssef L., additional

Published
2005
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49. Multipotent Adult Progenitor Cells Prevent Macrophage-Mediated Axonal Dieback and Promote Regrowth after Spinal Cord Injury.

Author

Busch, Sarah A., Hamilton, Jason A., Horn, Kevin P., Cuascut, Fernando X., Cutrone, Rochelle, Lehman, Nicholas, Deans, Robert J., Ting, Anthony E., Mays, Robert W., and Silver, Jerry

Subjects
SPINAL cord regeneration, MACROPHAGES, SPINAL cord injuries, IMMUNOMODULATORS, PROTEOGLYCANS, NEUROPLASTICITY
Abstract

Macrophage-mediated axonal dieback presents an additional challenge to regenerating axons after spinal cord injury. Adult adherent stem cells are known to have immunomodulatory capabilities, but their potential to ameliorate this detrimental inflammation-related process has not been investigated. Using an in vitro model of axonal dieback as well as an adult rat dorsal column crush model of spinal cord injury, we found that multipotent adult progenitor cells (MAPCs) can affect both macrophages and dystrophic neurons simultaneously. MAPCs significantly decrease MMP-9 (matrix metalloproteinase-9) release from macrophages, effectively preventing induction of axonal dieback. MAPCs also induce a shift in macrophages from an M1, or "classically activated" proinflammatory state, to an M2, or "alternatively activated" antiinflammatory state. In addition to these effects on macrophages, MAPCs promote sensory neurite outgrowth, induce sprouting, and further enable axons to overcome the negative effects of macrophages as well as inhibitory proteoglycans in their environment by increasing their intrinsic growth capacity. Our results demonstrate that MAPCs have therapeutic benefits after spinal cord injury and provide specific evidence that adult stem cells exert positive immunomodulatory and neurotrophic influences. [ABSTRACT FROM AUTHOR]

Published
2011
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