Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system

Lewis, Ian D.; Almeida-Porada, Graça; Du, Juan; Lemischka, Ihor R.; Moore, Kateri; Zanjani, Esmail D.; Verfaillie, Catherine M.

doi:10.1182/blood.v97.11.3441

Cited by 130 publications

(97 citation statements)

References 42 publications

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“…[23][24][25] Clinically, while the absence of durable engraftment from ex vivo-expanded CD34 þ cells has once been reported, 26 durable engraftment has been reported in patients who received expanded autologous peripheral blood progenitor cells as the sole source of hematopoietic support following high-dose therapy. 19 This observation, together with other evidence, suggests that the primitive HPC compartment, [27][28][29][30][31][32] HPC homing after transplantation 33 and basic biological and genetic characteristics of HPC, 34 are preserved following ex vivo expansion.…”

Section: Introductionmentioning

confidence: 91%

Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells

Robinson

Niu

et al. 2006

Bone Marrow Transplant

214

150

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One factor limiting the therapeutic efficacy of cord blood (CB) hematopoietic progenitor cell (HPC) transplantation is the low cell dose of the graft. This is associated with an increased incidence of delayed or failed engraftment. Cell dose can be increased and the efficacy of CB transplantation potentially improved, by ex vivo CB expansion before transplantation. Two ex vivo CB expansion techniques were compared: (1) CD133 þ selection followed by ex vivo liquid culture and (2) co-culture of unmanipulated CB with bone-marrow-derived mesenchymal stem cells (MSCs). Ex vivo culture was performed in medium supplemented with granulocyte colony-stimulating factor, stem cell factor and either thrombopoietin or megakaryocyte growth and differentiation factor. Expansion was followed by measuring total nucleated cell (TNC), CD133 þ and CD34 þ cell, colony-forming unit and cobblestone area-forming cell output. When compared to liquid culture, CB-MSC co-culture (i) required less cell manipulation resulting in less initial HPC loss and (ii) markedly improved TNC and HPC output. CB-MSC coculture therefore holds promise for improving engraftment kinetics in CB transplant recipients.

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Section: Introductionmentioning

confidence: 91%

Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells

Robinson

Niu

et al. 2006

Bone Marrow Transplant

214

150

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“…Furthermore, the progenitor cell content has been suggested as an improved predictor of transplant outcomes, 25 and the TNC dose has also been suggested to have an influence on lymphoid reconstitution. 40 Similar to others, we are investigating alternative strategies to increase the UCB cell dose, such as the double unit UCB transplant, ex vivo expansion 40,41 and co-infusion of mesenchymal stem cells. 37,42,43 …”

Section: Discussionmentioning

confidence: 99%

Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group

Petterson

Gabriel

Tiedemann

et al. 2008

Bone Marrow Transplant

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Unrelated umbilical cord blood (UCB) is an alternative stem cell source for paediatric patients lacking a matched related or unrelated marrow donor. We report the results of all paediatric unrelated UCB transplants performed in Australia and New Zealand over a 10-year period. A total of 135 patients were transplanted, 100 for malignant disease (74%) and 35 for non-malignant disorders. The majority (88%) of patients received an HLA-mismatched graft. The median infused total nucleated cell dose was 4.7 Â 10 7 /kg and CD34 þ count 1.9 Â 10 5 /kg. Neutrophil engraftment occurred in 83% of patients by day 42 (median 23 days) and platelet engraftment in 55% by day 60 (median 56 days). Grades II-IV and III-IV acute GVHD occurred in 41 and 18% of patients, respectively. TRM and overall survival 1-year post transplant were 32 and 61%, respectively. A higher probability of neutrophil recovery (P ¼ 0.004) and faster time to recovery (median 18 days vs 26 days, P ¼ 0.008) were observed in recipients of a cord unit with a CD34 cell dose X1.7 Â 10 5 /kg. Our results support selection of cord units with CD34 cell doses X1.7 Â 10 5 /kg to promote faster engraftment, improve survival and lower TRM.

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“…McNiece et al [20] have developed a two-step ex vivo culture procedure that results in the further expansion of CD34 + cells with a resulting enrichment for mature neutrophils comparable to cultures of ex vivo expanded peripheral blood progenitor cells. Furthermore, human CD34 + UCB cells expanded ex vivo without a murine stromal cell feeder layer have "long-term" engrafting potential as demonstrated by their ability to reconstitute primary and secondary nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice or preimmune fetal sheep [21]. Such "stroma free" systems are more adaptable for clinical use by avoiding complications from murine feeder cells.…”

Section: Transplantation With Ucb : Clinical Studiesmentioning

confidence: 99%

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

Brown

Boussiotis

2008

Clinical Immunology

152

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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Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system

Cited by 130 publications

References 42 publications

Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells

Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells

Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group

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

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