博文
胚胎干细胞药物（Prochymal）研究进展
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今年5月，美国FDA以孤儿药方式核准Osiris公司的Prochymal用于I型糖尿病的治疗。此外，该产品的其他适应症，如治疗克罗恩氏病、修复梗死心脏组织、胰岛细胞再生等也处于临床研究阶段。而且，Prochymal在2008年还拿到美国国防部2.2亿美元的合同，这是目前干细胞产业最昂贵的订单。
http://news.sciencenet.cn/htmlnews/2010/9/237185.shtm
全球首个胚胎干细胞药物
http://www.gopubmed.org/web/gopubmed/1?WEB1mOWEB10O00d000j10020001000h00100090000
Prochymal or GRNOPC1
documents
Title: Efficacy and Safety of Ex-vivo Cultured Adult Human Mesenchymal Stem Cells (Prochymal(TM)) in Pediatric Patients with Severe Refractory Acute Graft-Versus-Host Disease in a Compassionate Use study.
Authors: Prasad, Vinod K, Lucas, Kenneth G, Kleiner, Gary, Talano, Julie An M, Jacobsohn, David, Broadwater, Gloria, Monroy, Rod, Kurtzberg, Joanne
Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2010
Abstract: Preliminary studies using directed-donor ex-vivo expanded human mesenchymal stem cells (hMSCs) have shown promise in the treatment of acute graft-versus-host disease (aGvHD). However, their production is cumbersome and standardization difficult. We now describe the first experience of using a pre-manufactured, universal donor, formulation of hMSCs (Prochymal) in children (n=12; 10 boys; 9 Caucasian; age range, 0.4 to 15 years) with treatment resistant Grade III and IV aGvHD who received therapy on compassionate use basis between July 2005 and June 2007 at 5 transplant centers. All patients had stage 3 or 4 gut (GI) symptoms and half had additional liver and/or skin involvement. Disease was refractory to steroids in all cases and additionally to a median of 3 other immunosuppressive therapies. The hMSCs (8x10(6)cells/kg/dose in 2 patients and 2x10(6)cells/kg/dose in the rest) were infused intravenously over 1 hour twice a week for 4 weeks. Partial and Mixed responders received subsequent weekly therapy for 4 weeks. HLA or other matching was not needed. The hMSCs were started at a median of 98 days (range 45-237) post-transplant. A total of 124 doses were administered with a median of 8 doses (range 2 -21) per patient. Overall, 7 (58%) patients had complete response, 2 (17%) partial response and 3 (25%) mixed response. Complete resolution of GI symptoms occurred in 9 (75%) patients. Two patients relapsed after initial response and showed partial response to re-treatment. The cumulative incidence of survival at 100-day from the initiation of Prochymal therapy was 58%. Five of 12 patients (42%) were still alive after a median follow-up of 730 days (range, 527-1211) in surviving patients. No infusional or other identifiable acute toxicity was seen in any patient. Multiple infusions of hMSCs were well tolerated and appear to be safe in children. Clinical responses, particularly in the GI system were seen in the majority of children with severe refractory aGvHD. Given the favorable results observed in a patient population with an otherwise grave prognosis, we conclude that hMSCs hold potential for the treatment of aGVHD and should be further studied in phase III trials in pediatric and adult patients.
Affiliation: The Pediatric Blood and Marrow Transplant Program, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Wikipedia: Acute disease, Adult, Caring, Child, Children, Client, Colony-forming unit, Colony forming unit, Compassion, Concise, Data collection, Data source, Delton, Donor, Empathy, Graft-versus-host disease, Graft-vs-host disease, Graft Versus Host Disease, Graft vs host disease, Incidence, Intermediate mesoderm, Lateral plate mesoderm, Mesenchyma, Mesenchymal Stem Cell, Mesenchymal stem cells, Mesenchyme, Mesoderm, Mother cell, Organ donor, Paraxial mesoderm, Patient, Pediatrics, Progenitor cell, Prognosis, Recrudescence, Recurrence, Reference standard, Relapse, Respondent, Rest, Runt disease, Safety, Standardization, Standards, Stem Cell, Stem cell differentiation, Survey, Survey Methodology
Title: A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction.
Authors: Hare, J M, Traverse, J H, Henry, T D, Dib, N, Strumpf, R K, Schulman, S P, Gerstenblith, G, Demaria, A N, Denktas, A E, Gammon, R S, Hermiller, J B, Reisman, M A, Schaer, G L, Sherman, W
Journal: Journal of the American College of Cardiology, Vol. 54 (24): 2277-86, 2009
Abstract: OBJECTIVES: Our aim was to investigate the safety and efficacy of intravenous allogeneic human mesenchymal stem cells (hMSCs) in patients with myocardial infarction (MI). BACKGROUND: Bone marrow-derived hMSCs may ameliorate consequences of MI, and have the advantages of preparation ease, allogeneic use due to immunoprivilege, capacity to home to injured tissue, and extensive pre-clinical support. METHODS: We performed a double-blind, placebo-controlled, dose-ranging (0.5, 1.6, and 5 million cells/kg) safety trial of intravenous allogeneic hMSCs (Prochymal, Osiris Therapeutics, Inc., Baltimore, Maryland) in reperfused MI patients (n=53). The primary end point was incidence of treatment-emergent adverse events within 6 months. Ejection fraction and left ventricular volumes determined by echocardiography and magnetic resonance imaging were exploratory efficacy end points. RESULTS: Adverse event rates were similar between the hMSC-treated (5.3 per patient) and placebo-treated (7.0 per patient) groups, and renal, hepatic, and hematologic laboratory indexes were not different. Ambulatory electrocardiogram monitoring demonstrated reduced ventricular tachycardia episodes (p=0.025), and pulmonary function testing demonstrated improved forced expiratory volume in 1 s (p=0.003) in the hMSC-treated patients. Global symptom score in all patients (p=0.027) and ejection fraction in the important subset of anterior MI patients were both significantly better in hMSCs versus placebo subjects. In the cardiac magnetic resonance imaging substudy, hMSC treatment, but not placebo, increased left ventricular ejection fraction and led to reverse remodeling. CONCLUSIONS: Intravenous allogeneic hMSCs are safe in patients after acute MI. This trial provides pivotal safety and provisional efficacy data for an allogeneic bone marrow-derived stem cell in post-infarction patients. (Safety Study of Adult Mesenchymal Stem Cells [MSC] to Treat Acute Myocardial Infarction; NCT00114452).
Affiliation: Department of Medicine, Cardiovascular Division and the Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA. jhare@med.miami.edu
Pubmed MeSH: Double-Blind Method, Female, Humans, Infusions, Intravenous, Male, Mesenchymal Stem Cell Transplantation, Middle Aged, Myocardial Infarction
Wikipedia: Adult, Adult stem cell, Baltimore, Client, Colony-forming unit, Colony forming unit, ECG, EKG, Echocardiography, Electrocardiogram, Electrocardiography, Forced Expiratory Volume, Functional MRI, Hepatitis, Incidence, Infarction, Intermediate mesoderm, Laboratories, Laboratory, Lateral plate mesoderm, Lung function test, MRI scan, MR Spectroscopy, Magnetic Resonance, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, MarylanD, Mesenchyma, Mesenchymal Stem Cell, Mesenchymal stem cells, Mesenchyme, Mesoderm, Mother cell, Myocardial Infarction, Myocardial infarct, Myocardial infarctions, NMR Spectroscopy, NMR imaging, Nonoxynol, Nonoxynol-9, Nuclear Magnetic Resonance, Paraxial mesoderm, Patient, Progenitor cell, Pulmonary Function Test, Ritodrine, Ritodrine hydrochloride, Safety, Stem Cell, Stem cell differentiation, Stroke Volume, Tachyarrhythmia, Tachycardia, Tachycardia, ventricular, Therapeutic, Tissue, Transthoracic echocardiography, Treatment, Ventricular tachycardia, Yutopar, Zeugmatography
Title: Genzyme backs Osiris, despite Prochymal flop.
Authors: Allison, M
Journal: Nature biotechnology, Vol. 27 (11): 966-7, 2009
No abstract given.
Pubmed MeSH: Animals, Clinical Trials as Topic, Drug Industry, Graft vs Host Disease, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Treatment Failure, United States, United States Food and Drug Administration
Wikipedia: Back
Title: Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease.
Authors: Kebriaei, P, Isola, L, Bahceci, E, Holland, K, Rowley, S, McGuirk, J, Devetten, M, Jansen, J, Herzig, R, Schuster, M, Monroy, R, Uberti, J
Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
, Vol. 15 (7): 804-11, 2009
Abstract: The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them a rationale agent to investigate for graft-versus-host disease (GVHD). Human MSCs were used to treat de novo acute GVHD (aGVHD). Patients with grades II-IV GVHD were randomized to receive 2 treatments of human MSCs (Prochymal(R)) at a dose of either 2 or 8 million MSCs/kg in combination with corticosteroids. Patients received GVHD prophylaxis with tacrolimus, cyclosporine, (CsA) or mycophenolate mofetil (MMF). Study endpoints included safety of Prochymal administration, induction of response to Prochymal, and overall response of aGVHD by day 28, and long-term safety. Thirty-two patients were enrolled, with 31 evaluable: 21 males, 10 females; median age 52 years (range: 34-67). Twenty-one patients had grade II, 8 had grade III, and 3 had grade IV aGVHD. Ninety-four percent of patients had an initial response to Prochymal (77% complete response [CR] and 16% partial response [PR]). No infusional toxicities or ectopic tissue formations were reported. There was no difference with respect to safety or efficacy between the low and high Prochymal dose. In conclusion, Prochymal can be infused safely into patients with aGVHD and induces response in a high proportion of GVHD patients.
Affiliation: Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. pkebriae@mdanderson.org
Pubmed MeSH: Acute Disease, Adolescent, Adrenal Cortex Hormones, Adult, Aged, Cyclosporine, Female, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Immunosuppressive Agents, Male, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Middle Aged, Mycophenolic Acid, Tacrolimus
Wikipedia: Acute disease, Adrenal cortex hormones, Adult, Choristoma, Ciclosporin, Client, Colony-forming unit, Colony forming unit, Corticoids, Corticosteroids, Critique, Cyclosporin, Cyclosporin A, Cyclosporine, Cyclosporine A, Evaluation, Evaluation research, FK-506, FK506, FK 506, Graft-versus-host disease, Graft-vs-host disease, Graft Versus Host Disease, Graft vs host disease, Intermediate mesoderm, Lateral plate mesoderm, Mesenchyma, Mesenchymal Stem Cell, Mesenchymal stem cells, Mesenchyme, Mesoderm, Mother cell, Neoral, Paraxial mesoderm, Patient, Progenitor cell, Prograf, Prograft, Restasis, Runt disease, Safety, Sandimmune, Stem Cell, Stem cell differentiation, Tacrolimus, Tissue
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