Autologous Hematopoietic Stem Cell Transplantation as a Treatment Option for Aggressive Multiple Sclerosis

Pfender, Nikolai; Saccardi, Riccardo; Martin, Roland

doi:10.1007/s11940-013-0234-9

Cited by 27 publications

(18 citation statements)

References 32 publications

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“…43 Different conditioning regimens may diversely affect the immune system. [8][9][10] Mechanistic evaluations on the effects of AHSCT for MS are limited to thymic recovery and regulatory T-cell reconstitution.…”

Section: Discussionmentioning

confidence: 99%

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

Arruda

Lorenzi

Sousa

et al. 2014

Bone Marrow Transplant

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Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternative for multiple sclerosis (MS). Despite advances in clinical management, knowledge about mechanisms involved with clinical remission post transplantation is still limited. Abnormal microRNA and gene expression patterns were described in MS and have been suggested as disease biomarkers and potential therapeutic targets. Here we assessed T-and B-cell reconstitution, microRNAs and immunoregulatory gene expression after AHSCT. Early immune reconstitution was mainly driven by peripheral homeostatic proliferation. AHSCT increased CD4 + CD25 hi FoxP3 + regulatory T-cell counts and expression of CTLA-4 and GITR (glucocorticoid-induced TNFR) on CD4 + CD25 hi T cells. We found transient increase in exhausted PD-1 + T cells and of suppressive CD8 + CD28 − CD57 + T cells. At baseline, CD4 + and CD8 + T cells from MS patients presented upregulated miR-16, miR-155 and miR-142-3p and downregulated FOXP3, FOXO1, PDCD1 and IRF2BP2. After transplantation, the expression of FOXP3, FOXO1, PDCD1 and IRF2BP2 increased, reaching control levels at 2 years. Expression of miR-16, miR-155 and miR-142-3p decreased towards normal levels at 6 months post therapy, remaining downregulated until the end of follow-up. These data strongly suggest that AHSCT normalizes microRNA and gene expression, thereby improving the immunoregulatory network. These mechanisms may be important for disease control in the early periods after AHSCT.

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Section: Discussionmentioning

confidence: 99%

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

Arruda

Lorenzi

Sousa

et al. 2014

Bone Marrow Transplant

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“…High-dose immunosuppressive regimens, followed by autologous hematopoietic stem cell transplantation (AHSCT), have been used with satisfactory results, controlling or reducing disease progression in most patients with refractory disease (7)(8)(9)35,42).…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts

et al. 2015

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, due to an immune reaction against myelin proteins. Multipotent mesenchymal stromal cells (MSCs) present immunosuppressive effects and have been used for the treatment of autoimmune diseases. In our study, gene expression profile and in vitro immunomodulatory function tests were used to compare bone marrow-derived MSCs obtained from MS patients, at pre-and postautologous hematopoietic stem cell transplantation (AHSCT) with those from healthy donors. Patient MSCs comparatively exhibited i) senescence in culture; ii) similar osteogenic and adipogenic differentiation potential; iii) decreased expression of CD105, CD73, CD44, and HLA-A/B/C molecules; iv) distinct transcription at pre-AHSCT compared with control MSCs, yielding 618 differentially expressed genes, including the downregulation of TGFB1 and HGF genes and modulation of the FGF and HGF signaling pathways; v) reduced antiproliferative effects when pre-AHSCT MSCs were cocultured with allogeneic T-lymphocytes; vi) decreased secretion of IL-10 and TGF-b in supernatants of both cocultures (pre-and post-AHSCT MSCs); and vii) similar percentages of regulatory cells recovered after MSC cocultures. The transcriptional profile of patient MSCs isolated 6 months posttransplantation was closer to pre-AHSCT samples than from healthy MSCs. Considering that patient MSCs exhibited phenotypic changes, distinct transcriptional profile and functional defects implicated in MSC immunomodulatory and immunosuppressive activity, we suggest that further MS clinical studies should be conducted using allogeneic bone marrow MSCs derived from healthy donors. We also demonstrated that treatment of MS patients with AHSCT does not reverse the transcriptional and functional alterations observed in patient MSCs.

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“…Hematopoietic stem cell transplantation (HSCT) has been reviewed in detail elsewhere [112][113][114][115][116]. Studies on animal models showed that strong immunosuppression followed by syngeneic bone marrow transplantation can induce long term antigen-specific tolerance [117].…”

Section: Autologous Bone Marrow Transplantationmentioning

confidence: 99%

The future of multiple sclerosis treatments

Coclitu

Constantinescu

Tanasescu

2016

Expert Review of Neurotherapeutics

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Autologous Hematopoietic Stem Cell Transplantation as a Treatment Option for Aggressive Multiple Sclerosis

Cited by 27 publications

References 32 publications

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

Bone Marrow Mesenchymal Stromal Cells Isolated from Multiple Sclerosis Patients have Distinct Gene Expression Profile and Decreased Suppressive Function Compared with Healthy Counterparts

The future of multiple sclerosis treatments

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