Curative islet and hematopoietic cell transplantation in diabetic mice without toxic bone marrow conditioning

Chang, Charles; Bhagchandani, Preksha; Poyser, Jessica; Velasco, Brenda J.; Zhao, Weichen; Kwon, Hye-Sook; Meyer, Everett; Shizuru, Judith A.; Kim, Seung K.

doi:10.1016/j.celrep.2022.111615

Cited by 7 publications

(4 citation statements)

References 58 publications

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“…To track the fate of these compartments in vivo, we transplanted purified cells in recipient mice treated with a non-myeloablative (NMA) conditioning regimen ( Fig. 6 A ; Chang et al, 2022 ). Conditioning using injection of anti-CD117 (ACK) antibody combined with low-grade irradiation did not trigger a major inflammatory response, and as a consequence, we observed minimal hematopoietic alterations by flow cytometry ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For BM transplantation assay in NMA conditions ( Chang et al, 2022 ), CD45.1 + C57BL/6 mice were successively treated intraperitoneally with 500 mg diphenhydramine HCl (D3630; Sigma-Aldrich) and intravenously with 500 mg ACK2 anti-CD117 antibody (#BE0293; Bio X Cell) 6 d before transplantation. Mice were then irradiated 3 d before transplantation with 200 cGy (137Cs irradiator).…”

Section: Methodsmentioning

confidence: 99%

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Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions

Solomon,

Song,

Govindarajah

et al. 2023

Journal of Experimental Medicine

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The dynamics of the hematopoietic flux responsible for blood cell production in native conditions remains a matter of debate. Using CITE-seq analyses, we uncovered a distinct progenitor population that displays a cell cycle gene signature similar to the one found in quiescent hematopoietic stem cells. We further determined that the CD62L marker can be used to phenotypically enrich this population in the Flt3+ multipotent progenitor (MPP4) compartment. Functional in vitro and in vivo analyses validated the heterogeneity of the MPP4 compartment and established the quiescent/slow-cycling properties of the CD62L− MPP4 cells. Furthermore, studies under native conditions revealed a novel hierarchical organization of the MPP compartments in which quiescent/slow-cycling MPP4 cells sustain a prolonged hematopoietic activity at steady-state while giving rise to other lineage-biased MPP populations. Altogether, our data characterize a durable and productive quiescent/slow-cycling hematopoietic intermediary within the MPP4 compartment and highlight early paths of progenitor differentiation during unperturbed hematopoiesis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions

Solomon,

Song,

Govindarajah

et al. 2023

Journal of Experimental Medicine

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“…The most important function of the immune system is to recognize and eliminate invading antigens and malignant cells while maintaining immune tolerance to its own components. However, unrestricted immune system activation can lead to clinical disorders, including autoimmune diseases, solid organ transplantation (SOT), hematopoietic stem cell transplantation (HSCT) and allergic diseases ( Choi et al, 2020 ; Zhuang et al, 2021 ; Chang et al, 2022 ). By inducing immune tolerance, that is, by inducing specific tolerances to disease-inducing immune cells, the body can avoid inflammation while retaining its normal immune response to foreign substances ( Ezekian et al, 2018 ).…”

Section: The Role Of Immune Tolerancementioning

confidence: 99%

Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance

Lin,

Wang,

Yang

et al. 2023

Front. Bioeng. Biotechnol.

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Dendritic cells (DCs) are the major specialized antigen-presenting cells (APCs), play a key role in initiating the body’s immune response, maintain the balance of immunity. DCs can also induce immune tolerance by rendering effector T cells absent and anergy, and promoting the expansion of regulatory T cells. Induction of tolerogenic DCs has been proved to be a promising strategy for the treatment of autoimmune diseases, organ transplantation, and allergic diseases by various laboratory researches and clinical trials. The development of nano-delivery systems has led to advances in situ modulation of the tolerance phenotype of DCs. By changing the material composition, particle size, zeta-potential, and surface modification of nanoparticles, nanoparticles can be used for the therapeutic payloads targeted delivery to DCs, endowing them with great potential in the induction of immune tolerance. This paper reviews how nano-delivery systems can be modulated for targeted delivery to DCs and induce immune tolerance and reviews their potential in the treatment of autoimmune diseases, organ transplantation, and allergic diseases.

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“…The establishment of hematopoietic chimerism is a type of cell therapy that is effective in inducing antigenspecific tolerance in transplantation and autoimmunity. It refers to the transfer of allogenic cells or autologous cells that express the diseasecausing antigen(s) into appropriately conditioned recipients (19)(20)(21)(22). Transplantation of donor hematopoietic stem cells (HSC) has been investigated as a strategy for tolerance induction in transplantation and has successfully led to tolerance to kidney transplantation in pilot clinical trials (23).…”

Section: Introductionmentioning

confidence: 99%

Adoptive transfer of allergen-expressing B cells prevents IgE-mediated allergy

Prickler,

Baranyi,

Mengrelis

et al. 2023

Front. Immunol.

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IntroductionProphylactic strategies to prevent the development of allergies by establishing tolerance remain an unmet medical need. We previously reported that the transfer of autologous hematopoietic stem cells (HSC) expressing the major timothy grass pollen allergen, Phl p 5, on their cell surface induced allergen-specific tolerance in mice. In this study, we investigated the ability of allergen-expressing immune cells (dendritic cells, CD4+ T cells, CD8+ T cells, and CD19+ B cells) to induce allergen-specific tolerance in naive mice and identified CD19+ B cells as promising candidates for allergen-specific cell therapy.MethodsFor this purpose, CD19+ B cells were isolated from Phl p 5-transgenic BALB/c mice and transferred to naive BALB/c mice, pre-treated with a short course of rapamycin and an anti-CD40L antibody. Subsequently, the mice were subcutaneously sensitized three times at 4-week intervals to Phl p 5 and Bet v 1 as an unrelated control allergen. Allergen-expressing cells were followed in the blood to monitor molecular chimerism, and sera were analyzed for Phl p 5- and Bet v 1-specific IgE and IgG1 levels by RBL assay and ELISA, respectively. In vivo allergen-induced lung inflammation was measured by whole-body plethysmography, and mast cell degranulation was determined by skin testing.ResultsThe transfer of purified Phl p 5-expressing CD19+ B cells to naive BALB/c mice induced B cell chimerism for up to three months and prevented the development of Phl p 5-specific IgE and IgG1 antibody responses for a follow-up period of 26 weeks. Since Bet v 1 but not Phl p 5-specific antibodies were detected, the induction of tolerance was specific for Phl p 5. Whole-body plethysmography revealed preserved lung function in CD19+ B cell-treated mice in contrast to sensitized mice, and there was no Phl p 5-induced mast cell degranulation in treated mice.DiscussionThus, we demonstrated that the transfer of Phl p 5-expressing CD19+ B cells induces allergen-specific tolerance in a mouse model of grass pollen allergy. This approach could be further translated into a prophylactic regimen for the prevention of IgE-mediated allergy in humans.

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Curative islet and hematopoietic cell transplantation in diabetic mice without toxic bone marrow conditioning

Cited by 7 publications

References 58 publications

Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions

Slow cycling and durable Flt3+ progenitors contribute to hematopoiesis under native conditions

Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance

Adoptive transfer of allergen-expressing B cells prevents IgE-mediated allergy

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