Application of Stem Cell-Enriched Bone Marrow Transplants to Prevent the Development of Coronary Vascular Disease in WB/F1 Autoimmune-Prone Mice

1995 ◽  
Vol 770 (1 Bone Marrow T) ◽  
pp. 380-380
Author(s):  
R. P. KIRZNER ◽  
R. W. ENGELMAN ◽  
R. A. GOOD
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Vascular Disease ◽  
Bone Marrow Transplants ◽  
Coronary Vascular Disease

scholarly journals Cytomegalovirus-Specific T-Cell Immunity in Recipients of Autologous Peripheral Blood Stem Cell or Bone Marrow Transplants

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3873-3879 ◽  
Author(s):  
Pierre Reusser ◽  
Rudolf Attenhofer ◽  
Holger Hebart ◽  
Claudine Helg ◽  
Bernard Chapuis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Bone Marrow Transplants ◽  
Cmv Infection ◽  
Cell Immunity ◽  
Ctl Activity

Abstract The cytomegalovirus (CMV)-specific CD8+ cytotoxic T-lymphocyte (CTL) and CD4+ T-helper cell (Th) functions were characterized in 15 CMV seropositive recipients of autologous peripheral blood stem cell or bone marrow transplants. These immune functions were evaluated in peripheral blood specimens obtained before and at 1, 2, and 3 months after transplant. For study of CTL activity, blood mononuclear cells were cocultured with CMV-infected autologous fibroblasts for 2 weeks and then tested for cytotoxicity against CMV-infected or mock-infected autologous and HLA-mismatched fibroblasts. The Th response to CMV antigen was assessed by standard lymphoproliferative assay. CMV-specific CD8+ CTL and CD4+ Th responses were detectable in 12 (80%) and 14 (93%) patients, respectively, in the first 3 months after transplantation. A Th response to CMV was always present by the time of first CTL detection. During the posttransplant period, CMV infection occurred in 6 (40%) patients, and detection of CMV-specific CD8+ CTL activity was associated with protection from subsequent CMV infection (P = .002). Among CMV seropositive autograft recipients, CMV-specific CD8+ CTL and CD4+ Th responses are restored in a large proportion of patients in the first 3 months after transplantation, and the presence of a specific CD8+ CTL activity affords protection from CMV infection.

Pretransplant Conditioning with Campath-1H (Alemtuzumab) in Pediatric Matched Unrelated Bone Marrow Transplants - An Institutional Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4651-4651
Author(s):  
Amulya A. Nageswara ◽  
Riten Kumar ◽  
Julia A Gourde ◽  
Vilmarie Rodriguez ◽  
Shakila Khan
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Conditioning Regimen ◽  
Cell Depletion ◽  
Bone Marrow Transplants ◽  
T Cell Depletion ◽  
Hematopoietic Stem ◽  
Cmv Disease

Abstract Abstract 4651 Introduction Graft versus host disease remains a major cause of mortality and morbidity following matched unrelated hematopoietic stem cell transplantation. Campath-1H (Alemtuzumab) is a humanized monoclonal antibody to CD52, an antigen expressed on T and B lymphocytes, monocytes and natural killer cells and is thought to reduce GVHD incidence through in vivo T cell depletion. Through the same mechanism it can potentially increase the risk of relapse by reducing the graft vs. leukemia effect and also possibly increase the risk of infection due to delayed immune recovery. This study looks at our experience with Campath-1H substituted in place of the conventional anti-thymocyte globulin (ATG) in our transplant conditioning regimen. Patients and Methods This retrospective case study included 17 pediatric (9 male; 8 female) matched unrelated bone marrow transplants done in our institution between January 2003 and June 2009 with Campath-1H as part of the pretransplant conditioning regimen. The primary transplant indication was leukemia/lymphoma (n=9), MDS/ MDS evolving into AML (n= 3), severe aplastic anemia (n=4) and Fanconi anemia (n=1). The conditioning regimen included Campath-1H given with cytoxan/ total body irradiation (TBI) in 14 patients, fludarabine/ TBI in 2 patients, and melphalan/ fludarabine in 1 patient. Campath-1H dosing was body weight based: 3mg (if between 5-15kg), 5 mg (if between 16-30kg) and 10 mg (if >30 kg) and 3 doses were administered when underlying condition was a malignancy and 4 doses when it was a bone marrow failure state. The last dose was given at least 24 hours prior to the bone marrow/ peripheral stem cell infusion. GVHD prophylaxis was with tacrolimus/methotrexate (n=12), tacrolimus (n=4) and cyclosporine/methotrexate (n=1). Standard institutional infectious prophylaxis was followed. Results The median age at transplant was 12.2 years (range; 0.7-19.7 years). All but one patient engrafted with a median of 21 days (range; 14-25 days). 5 out of 17 developed Grade I-II acute GVHD which resolved with steroids. No patient developed chronic GVHD. One patient had a CMV reactivation but no patient developed active CMV disease. 4 patients had varicella one of whom died of disseminated infection (day +376). The same patient also had adeno viral infection and BK viremia. 1 patient developed PCP pneumonia and retinal toxoplasmosis. 5 patients (6 transplants) relapsed (range; 40-641 days) with 3 relapsing within +100 days. 1 patient developed PTLD which was successfully treated with rituximab. Of the 4 patient deaths 3 were due to relapse and one due to disseminated varicella infection. The median follow-up time was 719 days (range; 147-2175 days). Overall survival as calculated using the Kaplan-Meir analysis was 100 % at 100 days and 94% at 1 year. Event free survival censoring for death, relapse and rejection was 76% at 100 days and 64% at 1 year. Conclusions Based on our experience, Campath-1H used as part of pretransplant conditioning regimen in pediatric matched unrelated transplants seems to reduce the risk of serious GVHD. This is in concordance with other published literature. T cell depletion is considered to increase the risk of life threatening infections. Our study had one infection related death. There were no patients with active CMV disease. This may in part be attributed to strict prophylactic measures and increased surveillance. Longer duration of follow-up is required to adequately analyze the relapse rates. Also, given our small patient numbers the effect of primary disease state and stage on relapse could not be assessed. Larger studies in the pediatric population with longer duration of follow-up comparing Campath-1H with conventional regimens are required to further assess its role with regards to graft vs. leukemia effect and also to establish if the decreased incidence of GVHD is sustained in larger cohorts. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Plasminogen System in Regulating Stem Cell Mobilization

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yanqing Gong ◽  
Jane Hoover-Plow
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Circulation ◽  
Stem Cell Mobilization ◽  
Bone Marrow Niche ◽  
Bone Marrow Transplants ◽  
Cell Mobilization ◽  
Underlying Mechanisms ◽  
Regenerate Tissue ◽  
Stimulating Factor

The treatment of patients with hematopoietic progenitor and stem cells (HPSCs) to reconstitute hematopoiesis after myeloablative therapy or to repair ischemia after myocardial infarction has significantly improved clinical outcomes. Successful blood or bone marrow transplants require a sufficient number of HPSCs capable of homing to the injured site to regenerate tissue. Granulocyte-colony stimulating factor (G-CSF) is widely used clinically for stem cell mobilization. However, in some patients the response is poor, thus a better understanding of the mechanisms underlying G-CSF-regulated stem cell mobilization is needed. The pasminogen (Plg) system is the primary fibrinolytic pathway responsible for clot dissolution after thrombosis. Recent evidence suggests that Plg plays a pivotal role in stem cell mobilization from the bone marrow to the peripheral circulation, particularly in HPSC mobilization in response to G-CSF. This paper will discuss the potential mechanisms by which the Plg system regulates stem cell mobilization, focusing on stepwise proteolysis and signal transduction during HPSC egress from their bone marrow niche. Clear elucidation of the underlying mechanisms may lead to the development of new Plg-based therapeutic strategies to improve stem cell mobilization in treating hematological and cardiovascular diseases.

scholarly journals Cytomegalovirus-Specific T-Cell Immunity in Recipients of Autologous Peripheral Blood Stem Cell or Bone Marrow Transplants

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3873-3879 ◽  
Author(s):  
Pierre Reusser ◽  
Rudolf Attenhofer ◽  
Holger Hebart ◽  
Claudine Helg ◽  
Bernard Chapuis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Bone Marrow Transplants ◽  
Cmv Infection ◽  
Cell Immunity ◽  
Ctl Activity

The cytomegalovirus (CMV)-specific CD8+ cytotoxic T-lymphocyte (CTL) and CD4+ T-helper cell (Th) functions were characterized in 15 CMV seropositive recipients of autologous peripheral blood stem cell or bone marrow transplants. These immune functions were evaluated in peripheral blood specimens obtained before and at 1, 2, and 3 months after transplant. For study of CTL activity, blood mononuclear cells were cocultured with CMV-infected autologous fibroblasts for 2 weeks and then tested for cytotoxicity against CMV-infected or mock-infected autologous and HLA-mismatched fibroblasts. The Th response to CMV antigen was assessed by standard lymphoproliferative assay. CMV-specific CD8+ CTL and CD4+ Th responses were detectable in 12 (80%) and 14 (93%) patients, respectively, in the first 3 months after transplantation. A Th response to CMV was always present by the time of first CTL detection. During the posttransplant period, CMV infection occurred in 6 (40%) patients, and detection of CMV-specific CD8+ CTL activity was associated with protection from subsequent CMV infection (P = .002). Among CMV seropositive autograft recipients, CMV-specific CD8+ CTL and CD4+ Th responses are restored in a large proportion of patients in the first 3 months after transplantation, and the presence of a specific CD8+ CTL activity affords protection from CMV infection.

Sternal bone marrow is a suitable autologous cell source for cardiac stem cell therapies

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
M. Arar ◽  
A. Rotärmel ◽  
A.-K. Knoefel ◽  
H. Baraki ◽  
I. Kutschka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cardiac Stem Cell ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Autologous Cell ◽  
Cell Source

A pilot study with autologous bone marrow-derived stem cell therapy in patients with severe peripheral arterial disorder

2008 ◽  
Vol 149 (12) ◽  
pp. 531-540 ◽  
Author(s):  
Zoltán Boda ◽  
Miklós Udvardy ◽  
Katalin Farkas ◽  
Judit Tóth ◽  
László Jámbor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Pilot Study ◽  
Cell Therapy ◽  
Color Doppler ◽  
Autologous Bone Marrow ◽  
Thromboangiitis Obliterans ◽  
Arteriosclerosis Obliterans ◽  
Autologous Bone ◽  
Peripheral Arterial

Súlyos perifériás artériás érbetegségekben a gyógyszeres és/vagy érsebészeti beavatkozások kimerülését követően a tűrhetetlen fájdalom, kiterjedt végtagi fekélyek, gangraenák megszüntetésének egyetlen módja a végtag amputációja. Betegek és módszerek: A szerzők – hazánkban elsőként – 5 előrehaladott perifériás artériás érbetegben (1 arteriosclerosis obliterans és 4 thromboangiitis obliterans) autológ csontvelői eredetű őssejtterápiát végeztek. A csontvelői őssejteket (CD34+ sejtek) crista biopsia végzésével nyerték. Mágneses sejtszeparálással CD34+ sejtszuszpenziót állítottak elő. Meghatározták a CD34+, CD133+ és CD45± sejtek számát és arányát. Az őssejtszuszpenziót intramuscularis injekció formájában a beteg végtagba juttatták vissza. Betegenként 0,37–1,14 × 10 5 /kg őssejt visszaadására került sor. Betegeiket 12 hónapig követték. Vizsgálatok történtek a beavatkozás előtt és után (1, 3, 6, 9 és 12 hónappal). Klinikai vizsgálatok: nyugalmi fájdalom, dysbasiás távolság, ischaemiás fekélyek gyógyhajlama, boka-kar index. Laboratóriumi vizsgálatok: angiográfia (az őssejtterápia előtt és után 1 és 6 hónappal), duplex ultrahang- és lézer-Doppler-scan, transcutan oxigéntenzió mérése, az endothelfunkciók vizsgálata. Eredmények: A nyugalmi fájdalom mind az öt betegük esetében megszűnt. A dysbasiás távolság szignifikánsan nőtt (36/440 m). Három beteg végtagi ischaemiás fekélye begyógyult, egy beteg nagyméretű fekélye lényegesen kisebbé és felületesebbé vált, egy betegben a végtagi fekély nem változott. A kezelt oldalon a boka-kar index szignifikánsan nőtt (0,41/0,83) tizenkét hónappal az őssejtterápiát követően, s nem változott az ellenoldalon. Három betegben tapasztaltak számottevő változást angiográfiával az őssejtterápia után hat hónappal. Csak szerény javulást észleltek color-Doppler- és lézer-Doppler-vizsgálatokkal. Az őssejtterápia előtt és után 1, 6 és 12 hónappal a transcutan oxigéntenzió-értékek a lábháton 18,10/16,78/23,83/37,50 Hgmm-re, míg a lábszáron 36,66/31,25/45,00/37,30 Hgmm-re változtak. A makro- és mikrocirkulációs paraméterek nem mutattak javulást az őssejtterápiát követően 1 hónappal, azonban az őssejtterápia után 3, 6, 9 és 12 hónappal már mérhető javulást tapasztaltak. Szövődményt, mellékhatást nem észleltek. Következtetések: Klinikai eredményeik alapján az autológ csontvelői eredetű őssejtterápiát hatásosnak, tartósnak és biztonságosnak tartják előrehaladott perifériás artériás érbetegségben. Szükség van további klinikai tapasztalatgyűjtésre.

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