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T cell regeneration clinical trials

C A DiNicola, A Zand, D W Hommes
Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease...
May 2017: Expert Opinion on Biological Therapy
Myriam N Bouchlaka, Andrea B Moffitt, Jaehyup Kim, John A Kink, Debra D Bloom, Cassandra Love, Sandeep Dave, Peiman Hematti, Christian M Capitini
Mesenchymal stem cells (MSCs) have immunosuppressive and tissue repair properties, but clinical trials using MSCs to prevent or treat graft-versus-host disease (GVHD) have shown mixed results. Macrophages (MØs) are important regulators of immunity and can promote tissue regeneration and remodeling. We have previously shown that MSCs can educate MØs toward a unique anti-inflammatory immunophenotype (MSC-educated MØs [MEMs]); however, their implications for in vivo models of inflammation have not been studied yet...
February 28, 2017: Biology of Blood and Marrow Transplantation
Mohammed S Chaudhry, Enrico Velardi, Florent Malard, Marcel R M van den Brink
The success of allogeneic hematopoietic stem cell transplantation, a key treatment for many disorders, is intertwined with T cell immune reconstitution. The thymus plays a key role post allogeneic hematopoietic stem cell transplantation in the generation of a broad but self-tolerant T cell repertoire, but it is exquisitely sensitive to a range of insults during the transplant period, including conditioning regimens, corticosteroids, infections, and graft-versus-host disease. Although endogenous thymic repair is possible it is often suboptimal, and there is a need to develop exogenous strategies to help regenerate the thymus...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Geeta Shroff
BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD...
December 13, 2016: American Journal of Case Reports
Yozo Nakazawa, Satoshi Suzuki, Nobuhiro Nishio
Adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells has provided a major breakthrough in the treatment of hematological malignancies. In Japan, it is expected that CD19 CAR-T cell therapy will be introduced earlier in clinical B cell malignancy settings and/or that a novel CAR-T cell therapy will be developed for non-B cell malignancies. The "Act on the Safety of Regenerative Medicine" and the "Revised Pharmaceutical Affairs Act" were promulgated in 2014. Both Acts were very important to the introduction and development of CAR-T therapy in Japan...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Estella M Alonso, Simon P Horslen, Edward M Behrens, Edward Doo
Pediatric acute liver failure (PALF) is a potentially devastating condition that occurs in previously healthy children of all ages and frequently leads to a rapid clinical deterioration. An identified cause for liver injury is lacking in approximately 30% of cases. Children with undetermined diagnosis have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. A single-day workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases brought together clinicians and basic scientists to integrate aligned research findings and develop a foundation for new mechanistic studies and future treatment trials...
March 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Dominic K T Pang, Zengxuan Nong, Brian G Sutherland, Cynthia G Sawyez, Debra L Robson, Jelena Toma, J Geoffrey Pickering, Nica M Borradaile
Niacin can reduce vascular disease risk in individuals with metabolic syndrome, but in light of recent large randomized controlled trials outcomes, its biological actions and clinical utility remain controversial. Niacin can improve endothelial function, vascular inflammation, and vascular regeneration, independent of correcting dyslipidemia, in various lean rodent models of vascular injury. Here, we tested whether niacin could directly improve endothelial cell angiogenic function during combined exposure to excess fatty acids and hypoxia, and whether intervention with niacin during continued feeding of western diet could improve revascularization and functional recovery in obese, hyperlipidemic mice with peripheral ischemia...
June 2016: Pharmacology Research & Perspectives
Mohammed S Chaudhry, Enrico Velardi, Jarrod A Dudakov, Marcel R M van den Brink
As the primary site of T-cell development, the thymus plays a key role in the generation of a strong yet self-tolerant adaptive immune response, essential in the face of the potential threat from pathogens or neoplasia. As the importance of the role of the thymus has grown, so too has the understanding that it is extremely sensitive to both acute and chronic injury. The thymus undergoes rapid degeneration following a range of toxic insults, and also involutes as part of the aging process, albeit at a faster rate than many other tissues...
May 2016: Immunological Reviews
Rachele Ciccocioppo, Giuseppina Cristina Cangemi, Peter Kruzliak, Gino Roberto Corazza
Chronic inflammatory enteropathies, including celiac disease, Crohn's disease, and ulcerative colitis, are lifelong disabling conditions whose cure is still an unmet need, despite the great strides made in understanding their complex pathogenesis. The advent of cellular therapies, mainly based on the use of stem cells, represents a great step forward thanks to their multitarget strategy. Both hematopoietic stem cells (HSC) and mesenchymal stem/stromal cells (MSC) have been employed in the treatment of refractory cases with promising results...
June 2016: Stem Cells
P Gomes-Alves, M Serra, C Brito, C P Ricardo, R Cunha, M F Sousa, B Sanchez, A Bernad, M J T Carrondo, L Rodriguez-Borlado, P M Alves
Human cardiac stem/progenitor cells (hCPCs) have been shown to be capable to regenerate contractile myocardium. However, because of their relative low abundance in the heart, in vitro expansion of hCPC is mandatory to achieve necessary quantities for allogeneic or autologous cardiac regeneration therapy applications (10(6)-10(9) cells/patient). Up to now, cell number requirements of ongoing phase I/IIa trials have been fulfilled with production in static monolayer cultures. However, this manufacturing process poses critical limitations when moving to the following clinical phases where hundreds of patients will be enrolled...
May 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Kazuyoshi Aso, Akitoshi Tsuruhara, Kentaro Takagaki, Katsuyuki Oki, Megumi Ota, Yasuhiro Nose, Hideki Tanemura, Naoki Urushihata, Jinichi Sasanuma, Masayuki Sano, Atsuyuki Hirano, Rio Aso, Jerry R McGhee, Kohtaro Fujihashi
It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice...
2016: PloS One
Amir Nejad-Moghaddam, Yunes Panahi, Meghdad Abdollahpour Alitappeh, Hojat Borna, Mohammad Ali Shokrgozar, Mostafa Ghanei
According to significant improvements in the tissue engineering field over the past several years, lung tissue cells have recently attracted more attention due to the high prevalence and diversity in related diseases. However, selection of an appropriate cell type, screening of suitable conditions for growth and proliferation, as well as subsequent implantation into the body to repair and regenerate damaged tissues are considered as important issues in this context. It should also be noted that most studies have been described in animal models, but not in humans...
December 2015: Iranian Journal of Allergy, Asthma, and Immunology
T Poghosyan, J Catry, M Luong-Nguyen, P Bruneval, T Domet, L Arakelian, R Sfeir, L Michaud, V Vanneaux, F Gottrand, J Larghero, P Cattan
Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets...
February 2016: Journal of Visceral Surgery
Marta Pokrywczynska, Jan Adamowicz, Monika Czapiewska, Daria Balcerczyk, Arkadiusz Jundzill, Maciej Nowacki, Peter Petros, Tomasz Drewa
INTRODUCTION: Controversy exists regarding the therapeutic benefit of cell-based therapy in the treatment of stress urinary incontinence (SUI). AREAS COVERED: The aim of this systematic review was to evaluate evidence regarding the therapeutic effect and safety of cell-based therapy in the treatment of SUI and to propose a new approach to SUI treatment utilizing tissue engineering methodologies. We have thoroughly reviewed the literature using PubMed in order to identify only original, clinical studies involving cell therapy for SUI...
2016: Expert Opinion on Biological Therapy
Riccardo Schweizer, Vijay S Gorantla, Jan A Plock
PURPOSE OF REVIEW: Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications...
December 2015: Current Opinion in Organ Transplantation
Graham G Walmsley, Kshemendra Senarath-Yapa, Taylor L Wearda, Siddharth Menon, Michael S Hu, Dominik Duscher, Zeshaan N Maan, Jonathan M Tsai, Elizabeth R Zielins, Irving L Weissman, Geoffrey C Gurtner, H Peter Lorenz, Michael T Longaker
Cell-based therapy is an emerging paradigm in skeletal regenerative medicine. However, the primary means by which transplanted cells contribute to bone repair and regeneration remain controversial. To gain an insight into the mechanisms of how both transplanted and endogenous cells mediate skeletal healing, we used a transgenic mouse strain expressing both the topaz variant of green fluorescent protein under the control of the collagen, type I, alpha 1 promoter/enhancer sequence (Col1a1(GFP)) and membrane-bound tomato red fluorescent protein constitutively in all cell types (R26(mTmG))...
January 2016: Tissue Engineering. Part A
Elie El Agha, Djuro Kosanovic, Ralph T Schermuly, Saverio Bellusci
In its broad sense, regeneration refers to the renewal of lost cells, tissues or organs as part of the normal life cycle (skin, hair, endometrium etc.) or as part of an adaptive mechanism that organisms have developed throughout evolution. For example, worms, starfish and amphibians have developed remarkable regenerative capabilities allowing them to voluntarily shed body parts, in a process called autotomy, only to replace the lost parts afterwards. The bizarre myth of the fireproof homicidal salamander that can survive fire and poison apple trees has persisted until the 20th century...
May 2016: Seminars in Cell & Developmental Biology
B Wiernicki, N Rozwadowska, A Malcher, T Kolanowski, A Zimna, A Rugowska, M Kurpisz
BACKGROUND: Myocardial infarction (MI) and left ventricle remodeling (LVR) are two of the most challenging disease entities in developed societies. Since conventional treatment cannot fully restore heart function new approaches were attempted to develop new strategies and technologies that could be used for myocardial regeneration. One of these strategies pursued was a cell therapy--particularly applying skeletal muscle stem cells (SkMCs). METHODS AND RESULTS: Using NOD-SCID murine model of MI and human skeletal myoblast transplantation we were able to show that SkMC administration significantly affected gene expression profile (p<0...
January 1, 2016: International Journal of Cardiology
Brody Wehman, Osama T Siddiqui, Rachana Mishra, Sudhish Sharma, Sunjay Kaushal
Stem cell therapy has the optimistic goal of regenerating the myocardium as defined by re-growth of lost or destroyed myocardium. As applied to patients with heart failure, many confuse or limit the regenerative definition to just improving myocardial function and/or decreasing myocardial scar formation, which may not be the most important clinical outcome to achieve in this promising field of molecular medicine. Many different stem cell-based therapies have been tested and have demonstrated a safe and feasible profile in adult patients with heart failure, but with varied efficacious end points reported...
August 2015: Cardiology in the Young
Kristina Candido, Henry Soufi, Mausumi Bandyopadhyay, Subhajit Dasgupta
Multiple sclerosis (MS) is a female predominant autoimmune demyelinating disease of central nervous system. The proper etiology is not clear. The existing therapies with interferon beta (Betaseron, Rebif), glatiramer acetate (copolymer 1, copaxone) are found to be promising for MS patients. The alpha-4 integrin antagonist monoclonal antibody Natalizumab has been found to decrease brain inflammation in relapsing-remitting MS via inhibition of alpha-4 beta- 1 integrinmediated mode of action of antigen -primed T cells to enter into central nervous system through blood brain barrier...
2016: Mini Reviews in Medicinal Chemistry
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