Intravenous mesenchymal stromal cell therapy for inflammatory bowel disease: Lessons from the acute graft versus host disease experience

Conklin, Laurie S.; Hanley, Patrick J.; Galipeau, Jacques; Barrett, John; Bollard, Catherine M.

doi:10.1016/j.jcyt.2017.03.006

Cited by 9 publications

(6 citation statements)

References 119 publications

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“…Therefore, exploring alternative treatment options is urgently required in the clinic (Verstockt et al, 2018 ). Mesenchymal stromal cells (MSCs) have demonstrated great potential as a feasible and effective strategy in experimental models of IBD (Conklin et al, 2017 ; Ciccocioppo and Corazza, 2018 ). However, several preclinical studies have shown that only a low percentage of implanted MSCs can home to the injured tissue and survive in vivo , suggesting that the therapeutic action is unlikely to be due to replacement of diseased tissue (Wang et al, 2016 ; Lopez-Santalla et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis

et al. 2020

Front. Bioeng. Biotechnol.

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Section: Introductionmentioning

confidence: 99%

Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis

et al. 2020

Front. Bioeng. Biotechnol.

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“…HBMSCs are adult stem cells with multidirectional differentiation ability that can be induced into osteoblasts, chondroblasts, adipocytes, and other cells under different conditions [15,16]. Improving the osteogenic differentiation ability of bone marrow mesenchymal stem cells is the key to bone regeneration [17].…”

Section: Discussionmentioning

confidence: 99%

MiR-920 promotes osteogenic differentiation of human bone mesenchymal stem cells by targeting HOXA7

Zha

Wang

2020

J Orthop Surg Res

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Background: To explore the effect of miR-920 on osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) and the possible mechanism. Methods: Osteoporosis (OP) and healthy control bone tissues were collected, and the relative expression of miR-920 and HOXA7 was measured. hBMSCs were isolated and cultured in vitro. Alkaline phosphatase activity and miR-920 and HOXA7 relative expression were measured during osteogenic differentiation of hBMSCs. Then, bioinformatic analysis was performed to assess the potential mechanism of miR-920. MiR-920 mimic and inhibitor were introduced into hBMSCs by lipofection transfection and were used to investigate the effect of miR-920 on the osteogenic differentiation of hBMSCs. A dual luciferase reporter assay was used to identify whether the 3′UTR of HOXA7 mRNA was a direct target of miR-920. Western blotting was performed to assess whether miR-920 affected the MAPK signaling pathway. Results: We found that miR-920 was downregulated in OP patients compared with controls, while HOXA7 was upregulated, and miR-920 had a negative correlation with HOXA7 (r = − 0.859, P = 0.001). Moreover, miR-920 was increased during osteogenic differentiation of hBMSCs, while HOXA7 had the opposite tendency. Bioinformatic analysis revealed that there were a total of 207 target genes, and MAPK was a potential targeted signaling pathway. MiR-920 mimic significantly increased ALP activity, calcium deposition, osteoblastic protein expression (ALP and OSX), and p-p38 and p-JNK protein levels. Conclusion: Overall, miR-920 promotes osteogenic differentiation of hBMSCs by targeting HOXA7 through the MAPK signaling pathway.

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“…Corticosteroids are relatively non-specific in their effects and ideally more specific treatments would be preferred [ 17 , 35 ]. Alternative approaches used in treatment of steroid-resistant graft host disease may also be useful, e.g., adoptive transfer of mesenchymal stromal cells [ 36 , 37 ], although their activity is not well established for irAEs. There also appears to be some success in treatment of acute graft versus host disease with JAK/Stat inhibitors like ruxolitinib without major side effects [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report

McGuire

Shklovskaya

Edwards

et al. 2017

Cancer Immunol Immunother

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Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control. Mass cytometry allowed comprehensive phenotyping of circulating lymphocytes and revealed that CD4+ T cells were profoundly depleted by ATG, while CD8+ T cells, B cells, NK cells and monocytes were relatively spared. Multiple abnormalities in CD4+ T cell phenotype were stably present in the patient before disease onset. These included a population of CCR4−CCR6− effector/memory CD4+ T cells expressing intermediate levels of the Th1-related chemokine receptor CXCR3 and abnormally high multi-drug resistance type 1 transporter (MDR1) activity as assessed by a rhodamine 123 excretion assay. Expression of MDR1 has been implicated in steroid resistance and may have contributed to the severity and lack of a sustained steroid response in this patient. The number of CD4+ rhodamine 123-excreting cells was reduced > 3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve more specific immune suppression.Electronic supplementary materialThe online version of this article (10.1007/s00262-017-2107-7) contains supplementary material, which is available to authorized users.

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Intravenous mesenchymal stromal cell therapy for inflammatory bowel disease: Lessons from the acute graft versus host disease experience

Cited by 9 publications

References 119 publications

Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis

Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis

MiR-920 promotes osteogenic differentiation of human bone mesenchymal stem cells by targeting HOXA7

Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report

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