Effective Treatment of Severe Steroid-Resistant Acute Graft-Versus-Host Disease With Umbilical Cord-Derived Mesenchymal Stem Cells

Wu, Kang Hsi; Chan, Chin Kan; Tsai, Chris; Chang, Yu‐Hsu; Sieber, Martin; Chiu, Te-Fa; Ho, Ming Hua; Peng, Ching Tien; Wu, Han; Huang, Jing‐Long

doi:10.1097/tp.0b013e31821aba18

Cited by 121 publications

(104 citation statements)

References 22 publications

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“…However, this treatment needs to be optimized, combining it with the right immunosuppressive therapies. We need to learn more about the therapeutic potential of stromal cells in order to understand their mechanistic functions Adipose tissue 83,88 Umbilical cord 83,89 Placenta-derived decidua 83,90 Exosomes from stromal cells 76 Expansion media FCS 8,9,[82][83][84][85][86][87] Platelet lysate medium 83,85 AB serum 84 Regulatory T cells CD4 þ in the clinical setting. We have learnt that they are immunosuppressive and that they have regenerative properties, but so far these traits have only been confirmed in vitro.…”

Section: Discussionmentioning

confidence: 99%

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Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

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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.

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Section: Discussionmentioning

confidence: 99%

“…As an alternative to BM-derived MSCs, adipose tissue-, umbilical cord-or placental tissue-derived stromal cells have been used for the treatment of acute GVHD 88,89 (Table 5).…”

Section: Alternate Sources Of Cells For Acute Gvhdmentioning

confidence: 99%

Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

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“…In addition, UCB-MSCs have a longer culture period and higher proliferation capacity than BM-MSCs. [26][27][28] Wu et al 15 reported that UCB-MSCs are more immunossupressive than BMMSCs. In animal models, MSCs from BM or UCB have been shown to enhance engraftment of donor HSCs after co-transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…13,14 In addition, several studies using third-party MSCs suggest that infusion of third-party MSCs are feasible. 13,15,16 Therefore, these findings provide attractive possibilities for the use of universal donor MSCs. MSCs can be isolated from various human tissues other than BM, among which UCB is obtained without invasive methods, and thus may be a more appropriate source of third-party MSCs.…”

Section: Introductionmentioning

confidence: 99%

Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation

Lee

Yoo

et al. 2013

Bone Marrow Transplant

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Success of umbilical cord blood transplantation (UCBT) has been limited by a high rate of graft failure and delayed hematological recovery. It has been postulated that MSCs have hematopoiesis-supportive properties. Therefore, to overcome the limitation of UCBT, third-party UCB-derived MSCs were co-transplanted in recipients receiving unrelated UCBT. Seven patients received UCB and third-party UCB-MSCs. Hematopoietic recovery and transplantation outcomes were compared with historic controls. There was no acute toxicity associated with the infusion of MSCs. The median day to neutrophil engraftment was 19 days in patients, as compared with 24 days in controls (P ¼ 0.03). The median day of platelet engraftment was 47 days and 57 days in patients and controls, respectively (P ¼ 0.26). In addition, there was no engraftment failure in the MSC group. The incidence of acute and chronic GVHD was comparable between the two groups. However, veno-occlusive disease and TRM did not occur in the MSC group. Thirdparty UCB-MSCs infusion was safe and feasible. MSCs may also enhance the engraftment of UCBT and prevent rejection. In addition, MSCs may have a role in decreasing TRM. Randomized, controlled trials are required to confirm these results and longer follow-up will determine the effects of MSCs on the risk of relapse.

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“…These could be strong candidates of alternative sources of MSCs. There are only a few small pilot studies of MSC therapy using an alternative source for refractory acute GVHD [54,55]. In the near future, embryonic stem cells [56] and induced pluripotent stem cells [57] could be available for MSC source.…”

Section: Problems and Future Directions Of Msc Therapy For Acute Gvhdmentioning

confidence: 99%

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Yoshioka¹,

Miura²

2016

Transl Med

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Acute graft versus host disease (GVHD) is the most critical complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The understanding of major histocompatibility complex (MHC) and the development of acute GVHD prophylaxis have contributed to decreasing the incidence of severe acute GVHD. However, these progresses expand the chance of receiving allo-HSCT from human leukocyte antigen (HLA) mismatched donor. In addition, the expanding of indication for allo-HSCT to elderly patients or patients with organ dysfunction by the pervasiveness of reduced-intensity conditioning is associated with increased risk of acute GVHD. Unexpectedly, severe refractory acute GVHD can occur even in allo-HSCT from HLA matched sibling donor. The first line therapy for severe acute GVHD is corticosteroid, but the second line therapy has not been established and the prognosis of steroid-resistant acute GVHD remains poor. Recently, the efficacy of human bone marrow mesenchymal stem cell (MSC) therapy for steroid-resistant acute GVHD has been consistently reported. MSCs are approved as a cell therapy drug for steroid-resistant acute GVHD in some countries. We here review the history and the future of MSC therapy for acute GVHD.

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Effective Treatment of Severe Steroid-Resistant Acute Graft-Versus-Host Disease With Umbilical Cord-Derived Mesenchymal Stem Cells

Cited by 121 publications

References 22 publications

Stromal cells–are they really useful for GVHD?

Stromal cells–are they really useful for GVHD?

Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

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