Expansion of LTC‐ICs and Maintenance of p21 and BCL‐2 Expression in Cord Blood CD34
            <sup>+</sup>
            /CD38
            <sup>−</sup>
            Early Progenitors Cultured over Human MSCs as a Feeder Layer

Kadereit, Suzanne; Deeds, Linda; Haynesworth, Stephen E.; Koç, Omer N.; Kozik, M.; Szekely, Emese; Daum-Woods, Kathleen; Goetchius, Glenn W.; Fu, Pingfu; Li, Renhao; Murphy, William J.; Laughlin, Mary J.

doi:10.1634/stemcells.20-6-573

Cited by 105 publications

(63 citation statements)

References 42 publications

(51 reference statements)

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“…Based on preliminary studies in our laboratory and results of other teams, 13,15,16,18 we developed a model of CD34 þ cell and MSC coculture and then cografting. MSCs are multipotent cells present in various adult tissues including the BM as well as in fetal tissues such as lung.…”

Section: Discussionmentioning

confidence: 99%

“…As stromal and endothelial cells have been proposed for some years to sustain HSPCs during culture and are suspected to enhance hematopoietic recovery after cografting in preclinical or clinical models, [11][12][13][14][15][16][17] we evaluated the potential usefulness of MSCs in the ACT context. We have previously shown the capacity of MSCs to cooperate with 4F to reduce apoptosis of CD34 þ cells exposed to doses up to 4 Gy in vitro and to preserve their hematopoietic potential in vitro.…”

mentioning

confidence: 99%

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Mesenchymal stem cells rescue CD34+ cells from radiation-induced apoptosis and sustain hematopoietic reconstitution after coculture and cografting in lethally irradiated baboons: is autologous stem cell therapy in nuclear accident settings hype or reality?

Drouet

Mourcin

Grenier

et al. 2005

Bone Marrow Transplant

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Summary:Autologous stem cell therapy (ACT) has been proposed to prevent irradiated victims from bone marrow (BM) aplasia by grafting hematopoietic stem and progenitor cells (HSPCs) collected early after damage, provided that a functional graft of sufficient size could be produced ex vivo. To address this issue, we set up a baboon model of cell therapy in which autologous peripheral blood HSPCs collected before lethal total body irradiation were irradiated in vitro (2.5 Gy, D 0 1 Gy) to mimic the cell damage, cultured in small numbers for a week in a serumfree medium in the presence of antiapoptotic cytokines and mesenchymal stem cells (MSCs) and then cografted. Our study shows that baboons cografted with expanded cells issued from 0.75 and 1 Â 10 6 /kg irradiated CD34 þ cells and MSCs (n ¼ 2) exhibited a stable long-term multilineage engraftment. Hematopoietic recovery became uncertain when reducing the CD34 þ cell input (0.4 Â 10 6 /kg CD34 þ cells; n ¼ 3). However, platelet recovery was accelerated in all surviving cografted animals, when compared with baboons transplanted with unirradiated, unmanipulated CD34 þ cells (0.5-1 Â 10 6 / kg, n ¼ 4). Baboons grafted with MSCs alone (n ¼ 3) did not recover. In all cases, the nonhematopoietic toxicity remained huge. This baboon study suggests that ACT feasibility is limited.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Mesenchymal stem cells rescue CD34+ cells from radiation-induced apoptosis and sustain hematopoietic reconstitution after coculture and cografting in lethally irradiated baboons: is autologous stem cell therapy in nuclear accident settings hype or reality?

Drouet

Mourcin

Grenier

et al. 2005

Bone Marrow Transplant

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“…These may include reduced graft lymphocyte numbers, altered recognition of recipient self antigens by UCB donor T cells interacting with recipient's antigenpresenting cells (APC) and limited response of these naive donor T cells activated by recipient alloantigen. Subsequently, these changes will result in impaired cytokine production, limited cellular activation and lack of clonal expansion of alloreactive T cells [29][30][31].…”

Section: Ucb Basic Biology and Implications For The Development Of Gvmentioning

confidence: 99%

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Brown

Boussiotis

2008

Clinical Immunology

151

112

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Allogeneic stem cell transplantation has continued to evolve as a common procedure for the treatment of hematological malignancies and bone marrow failure. Donor bone marrow and mobilized peripheral stem cells are routinely employed for the reconstitution of immune function in leukemia and lymphoma patients following radiation and/or chemotherapy. Unfortunately, only 30% of patients have an HLA identical sibling donor and the identification of matched unrelated donors, particularly for minorities, can present an exceptional challenge. The transplantation of umbilical cord blood (UCB) represents the most recent strategy to expand the potential donor pool while maintaining an acceptable level of treatment related complications. First utilized in children, UCB transplantation permits a higher degree of HLA disparity while demonstrating a reduction in the incidence and severity of graft versus host disease (GvHD) compared to previous transplantation modalities. Despite the apparent decrease in GvHD, relapse rates remain comparable to transplantation with bone marrow or mobilized peripheral blood suggesting a strong graft versus leukemia/lymphoma (GvL) effect. However, several issues complicate the use of UCB transplantation and its extension to the treatment of adults. Many infections that afflict transplant patients are particularly frequent and more severe in the context of UCB transplantation. UCB T cells are naïve and therefore display less proliferation and IFN-γ production in response to cognate antigen and also appear to demonstrate defects in signal transduction mechanisms. In addition, UCB contain T regulatory cells (Treg) with more potent suppressor function than adult Treg. Furthermore, adult patients often require more total cells and CD34+ progenitors for transplantation than a single UCB unit can provide. Thus, strategies to expand selected subpopulations from UCB and the use of multiunit transplantation are areas of active research. This review will provide a condensed summary of the clinical history of UCB transplantation and emphasize the advantages and disadvantages of this approach to hematological malignancies in comparison to other methods of hematopoietic stem cell transplantation. Subsequently, it will mainly focus on the current challenges to immune reconstitution presented by UCB transplantation, recent research into their cellular and molecular mechanisms, and experimental approaches to overcome them.

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“…14 Moreover, mesenchymal stem cells present in cord blood could also account for a reduced apoptosis or increased proliferation of CD34 þ cells. 15 The idea of antiapoptotic factors in samples stored at RT is also supported by the apoptosis analysis and clonogenicity data: storage at RT did not increase the apoptosis rate, while after 24 h at 4 1C more cells stained positive for annexin, a marker for early apoptosis. 11 The apoptosis rate decreased with storage time indicating that early apoptotic cells probably died off within 24 h and were removed by Ficoll the following day.…”

Section: Discussionmentioning

confidence: 84%

Optimum storage conditions for cord blood-derived hematopoietic progenitor cells prior to isolation

Moldenhauer

Wolf

Habermann

et al. 2007

Bone Marrow Transplant

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Optimum storage conditions of cord blood-derived hematopoietic progenitor cells before isolation remain unknown. We therefore evaluated CD34 þ cells isolated from cord blood units (n ¼ 57) within 1 h after collection and following storage for 24, 48 and 72 h at either room temperature (RT) or 4 1C. Isolated CD34 þ cells were analyzed for their cell count, immunophenotype, apoptosis rate, clonogenicity and transmigration capacity in response to stromaderived factor 1a using direct-paired comparisons (n ¼ 27). CD34 þ , CD133 þ and CD45 þ positivity after isolation remained the same under all conditions. After 24 h, CD34 þ cell counts and numbers of CFU-GM colonies dropped regardless of the storage temperature. After 48 h, the number of CD34 þ cells increased compared to 24 h, if the cord blood had been stored at RT resulting in almost three times more CD34 þ cells than at 4 1C. These cells had a lower early apoptosis rate and formed four times more BFU-E than those stored at 4 1C with equivalent plating efficiencies. CD34 þ cells kept at RT for 48 h had the highest transmigration capacities, which paralleled an increased CXCR-4 expression. Cord blood should be stored at RT before CD34 þ isolation and a storage time for 48 h should be preferred to 24 h.

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Expansion of LTC‐ICs and Maintenance of p21 and BCL‐2 Expression in Cord Blood CD34 ⁺ /CD38 ⁻ Early Progenitors Cultured over Human MSCs as a Feeder Layer

Abstract: ABSTRACT

Cited by 105 publications

References 42 publications

Mesenchymal stem cells rescue CD34+ cells from radiation-induced apoptosis and sustain hematopoietic reconstitution after coculture and cografting in lethally irradiated baboons: is autologous stem cell therapy in nuclear accident settings hype or reality?

Mesenchymal stem cells rescue CD34+ cells from radiation-induced apoptosis and sustain hematopoietic reconstitution after coculture and cografting in lethally irradiated baboons: is autologous stem cell therapy in nuclear accident settings hype or reality?

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Optimum storage conditions for cord blood-derived hematopoietic progenitor cells prior to isolation

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Expansion of LTC‐ICs and Maintenance of p21 and BCL‐2 Expression in Cord Blood CD34 + /CD38 − Early Progenitors Cultured over Human MSCs as a Feeder Layer

Abstract: ABSTRACT

Cited by 105 publications

References 42 publications

Mesenchymal stem cells rescue CD34+ cells from radiation-induced apoptosis and sustain hematopoietic reconstitution after coculture and cografting in lethally irradiated baboons: is autologous stem cell therapy in nuclear accident settings hype or reality?

Mesenchymal stem cells rescue CD34+ cells from radiation-induced apoptosis and sustain hematopoietic reconstitution after coculture and cografting in lethally irradiated baboons: is autologous stem cell therapy in nuclear accident settings hype or reality?

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Optimum storage conditions for cord blood-derived hematopoietic progenitor cells prior to isolation

Contact Info

Product

Resources

About

Expansion of LTC‐ICs and Maintenance of p21 and BCL‐2 Expression in Cord Blood CD34 ⁺ /CD38 ⁻ Early Progenitors Cultured over Human MSCs as a Feeder Layer