Cotransplantation of ex vivo–expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation

Ball, Lynne M.; Bernardo, Maria Ester; Roelofs, Helene; Lankester, Arjan C.; Cometa, Angela; Egeler, R. Maarten; Locatelli, Franco; Fibbe, Willem E.

doi:10.1182/blood-2007-04-087056

Cited by 489 publications

(400 citation statements)

References 9 publications

Supporting

Mentioning

380

Contrasting

Unclassified

Order By: Relevance

“…Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential, together with their effects on immune responses, make them a promising therapeutic tool for severe refractory autoimmune diseases. MSCs have already been used in clinical trials as a treatment for acute graft-versus-host disease following allogeneic HSCT (25,26) and for autoimmune diseases such as systemic sclerosis (27) and type 1 diabetes mellitus (28).…”

Section: Discussionmentioning

confidence: 99%

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

Sun

Wang

Liang

et al. 2010

Arthritis & Rheumatism

428

310

View full text Add to dashboard Cite

Objective. Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self-renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment-refractory systemic lupus erythematosus (SLE).Methods. We conducted a single-arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life-threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines.Results. From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3-28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti-dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re-established balance between Th1-and Th2-related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths.Conclusion. Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment-refractory SLE.Systemic lupus erythematosus (SLE) is an inflammatory disease with protean manifestations, ranging from relatively minor skin and joint symptoms to severe life-threatening major organ involvement, such as nephritis and neuropsychiatric complications (1). It is characterized by the presence of autoreactive T and B lymphocytes, with polyclonal activation of B cells and the consequent production of autoantibodies by plasma ClinicalTrials.gov identifier: NCT00698191.

show abstract

Section: Discussionmentioning

confidence: 99%

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

Sun

Wang

Liang

et al. 2010

Arthritis & Rheumatism

428

310

View full text Add to dashboard Cite

show abstract

“…Bernardo et al 96 used MSCs at the time of HSCT transplantation in children who were recipients of cord blood grafts. Ball et al 97 performed co-transplantation of MSCs in children undergoing haploidentical HSCT. Compared with retrospective controls, they saw less graft failure and faster engraftment of platelets using MSCs.…”

Section: Stromal Cells For Prevention Of Gvhdmentioning

confidence: 99%

Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

View full text Add to dashboard Cite

Mesenchymal stromal cells (MSCs) have immunomodulatory effects and are increasingly being used for the treatment of acute and chronic GVHD. Although they seem immuno-privileged, they induce alloresponses, but the risk of immunization is poorly characterized. After infusion, they first reach the lungs, liver and spleen, and are then difficult to trace. Several mechanisms are involved in stromal cells suppressing alloreactivity, such as induction of regulatory T cells, but whether or not this will also affect leukemic relapse or increase infections is not known. Although several encouraging pilot studies have been published, there have been few prospective randomized trials. There may be a bias in the literature, as negative results are seldom published, and there have been few comparative studies with other immunosuppressive regimens. Most animal models have failed to show any effect on GVHD. Several questions remain to be answered for optimization of stromal cell therapy. Which source is optimal-BM, fat, cord or decidua? Can stromal cells be replaced by exosomes, which culture conditions are most appropriate and at what passage and how frequently should cells be administered? More research is required to move stromal cell therapy forward to become an established treatment for acute and chronic GVHD.

show abstract

“…[22][23][24] After haploidentical SCT, co-transplantation with MSCs enhanced NK-cell but not neutrophil or platelet recovery. 25 In vitro, MSCs have antiproliferative properties that target virtually all types of immune cells. Accordingly, human MSCs suppress lymphocyte alloreactivity when added in MLRs.…”

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%

“…26,27 Co-infusion of MSCs reduced the incidence of graft failure and rejection in preliminary clinical trials. 24,25 In a phase-I study, the incidence of acute GVHD grade II-IV was observed in 28% of patients co-administered with culture-expanded MSCs and HLA-identical sibling-matched HSCs. 23 However, whether MSCs exert preventive effects on the development of GVHD as well as therapeutic effects in established GVHD needs to be evaluated in prospective clinical trials.…”

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%

Prophylaxis of acute GVHD: manipulate the graft or the environment?

Barrett

Blanc

2008

Best Practice & Research Clinical Haematology

View full text Add to dashboard Cite

Graft-versus-host disease (GVHD) is the immune response of donor T lymphocytes responding to the recipient's alloantigens. The cellular and cytokine mechanisms driving GVHD are now well defined and have led to several prophylactic approaches. Selective allodepletion techniques promise to prevent GVHD without causing immune deficiency provoked by global T-cell depletion. Targeted dosing other (non-T-cells) cells in the graft -such as CD34 + progenitors, regulatory T cells, natural killer cells and mesenchymal stromal cells -can also lead to transplants designed to retain immune capability without causing GVHD. Immunosuppressive drugs such as methotrexate, cyclosporine and anti-lymphocyte antibodies are the mainstay in the prevention of GVHD and can be used in conjunction with engineered grafts to eliminate GVHD. In future it is anticipated that further refinements in targeting the elimination or suppression of GVHD reacting T cells should be selective enough to preserve the important graft-versus-leukemia effect which contributes to the cure of malignant diseases by allogeneic stem-cell transplantation. Keywords selective T-cell depletion; regulatory T cells; natural killer cells; mesenchymal stromal cells; calcineurin inhibitors; graft-versus-leukemiaWhile the classic rules of the conditions necessary for GVHD development proposed by Billingham remain as valid today as they did when he proposed them, we have since greatly refined our understanding of the positive and negative factors influencing the development of GVHD. 1 Figure 1 summarizes factors regulating the development of acute GVHD. This schema identifies key events leading to GVHD which are susceptible to therapeutic intervention to prevent GVHD. GVHD development can be interrupted at two distinct stages: (1) selection of the cells to be engrafted, and (2) modulation of the post-transplant milieu.

show abstract

Cotransplantation of ex vivo–expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation

Cited by 489 publications

References 9 publications

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

Stromal cells–are they really useful for GVHD?

Prophylaxis of acute GVHD: manipulate the graft or the environment?

Contact Info

Product

Resources

About