Ex Vivo Expansion of Human Umbilical Cord Blood-Derived T-Lymphocytes with Homologous Cord Blood Plasma

Kim, Yong‐Man; Jung, Minji; Song, Heon; Yang, Hyun Ok; Lee, Sung-Tae; Kim, Jong-Hyeok; Kim, Young‐Tak; Nam, Joo‐Hyun; Mok, Jung Eun

doi:10.1620/tjem.205.115

Cited by 16 publications

(19 citation statements)

References 19 publications

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“…Also, IL‐16 cytokine, a modulator of T cell activation, has been detected in CBP and potentially presents a physiological mechanism for foetal‐maternal tolerance. Due to CBP's specific molecular composition, numerous studies showed beneficial effect of CBP in replacement of standard FBS for various cell expansions in vitro, which may be essential to achieve appropriate cell numbers for clinical use.…”

Section: Discussionmentioning

confidence: 99%

“…Cord blood plasma (CBP) is commonly obtained from human umbilical cord blood (hUCB) during cell isolation and has mainly been considered a waste product. However, the trophic effect of CBP has been shown in replacing standard serum during the expansion of hUCB‐derived mesenchymal stem cells, human dental stem cells, hUCB‐derived T‐lymphocytes, or human endothelial colony‐forming cells in vitro. Moreover, the therapeutic potential of CBP administration into rats modelling acute ischaemic stroke was demonstrated by enhancement of neurogenesis and reduction of inflammation leading to significant post‐stroke functional recovery .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma derived from human umbilical cord blood: Potential cell‐additive or cell‐substitute therapeutic for neurodegenerative diseases

Ehrhart

Sanberg

Garbuzova‐Davis

2018

J Cellular Molecular Medi

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Limited efficacy of current therapeutic approaches for neurodegenerative disease has led to increased interest in alternative therapies. Cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may be a potential therapeutic. Benefits of CBP injection into rodent models of aging or ischaemic stroke have been demonstrated, though how benefits are elicited is still unclear. The present study evaluated various factors within the same samples of CBP and human adult blood plasma/sera (ABP/S). Also, autologous CBP effects vs. ABP/S or foetal bovine serum supplements on mononuclear cells from hUCB (MNC hUCB) in vitro were determined. Results showed significantly low concentrations of pro‐inflammatory cytokines (IL‐2, IL‐6, IFN‐γ, and TNF‐α) and elevated chemokine IL‐8 in CBP. Significantly higher levels of VEGF, G‐CSF, EGF and FGF‐basic growth factors were determined in CBP vs. ABP/S. Autologous CBP media supplements significantly increased MNC hUCB viability and decreased apoptotic cell activity. We are first to demonstrate the unique CBP composition of cytokines and growth factors within the same CBP samples derived from hUCB. Also, our novel finding that autologous CBP promoted MNC hUCB viability and reduced apoptotic cell death in vitro supports CBP's potential as a sole therapeutic or cell‐additive agent in developing therapies for various neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma derived from human umbilical cord blood: Potential cell‐additive or cell‐substitute therapeutic for neurodegenerative diseases

Ehrhart

Sanberg

Garbuzova‐Davis

2018

J Cellular Molecular Medi

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“…Lam et al (2001) have used cord blood plasma for the expansion of cord blood HSC. The cord blood plasma has also been used to culture T cells for adoptive immunotherapy (Kim et al, 2005). Shetty et al (2007) reported that human umbilical cord blood serum can replace fetal bovine serum in the culture of mesenchymal stem cells.…”

Section: Discussionmentioning

confidence: 99%

Optimization of Culture Conditions to Support Undifferentiated Growth of Human Embryonic Stem Cells

Lai

Cheng²,

Liu³

et al. 2010

Cellular Reprogramming

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Human embryonic stem cells (hESCs) are usually maintained in an undifferentiated state by coculture with mitomycin C-treated mouse embryonic fibroblasts (MEFs) as feeder cells in the presence of animal sera such as fetal bovine serum (FBS). Here, we use primary human amnion epithelial cells (hAECs) as feeder cells and human umbilical cord blood serum (CBS) as a replacement for FBS to support undifferentiated growth of hESCs. The 5 approximately 10-fold higher expression levels of ES cell markers including FGF, Oct-4, Nanog, Sox-2, Rex, and TERT were found in hESCs grown on hAECs compared with that on MEFs as measured by quantitative real-time polymerase chain reaction (PCR). By immunofluorescence, the expresisons of Oct-4 and Nanog is also higher in cells grown on hAECs than those on MEFs. Importantly, the ES cells grown on hAECs exhibit normal karyotypes on passage 25, thus ruling out the possibility of transformation. Using flow cytometry analysis, we show that both the ES cells grown on hAECs and MEFs have the same cell cycle distribution pattern. Further, hESCs cultured on hAECs for at least 20 passages could differentiate into three germ layers via teratoma formation. In addition, chromatin immunoprecipitation assay revealed that histone H3 is highly acetylated, and H3 lysine (K) 4 is hypermethylated at the Nanog locus and the Oct-4 locus in hESCs grown on hAECs. Conversely, hESCs grown on MEFs show histone deacetylation and H3-K4 demethylation. Taken together, these results suggest that hAECs supplemented with 10% CBS are suitable for hESC culture, and that this method may prove to be valuable for use in future regenerative therapies.

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“…While UCB-derived T cells can be propagated ex vivo, [43][44][45][46][47][48][49] the functional immaturity of T cells in circulating umbilical cord blood typically prevents ex vivo identification of endogenous leukemia/ lymphoma-specific T cells. Therefore, we developed a genetic engineering strategy to introduce a chimeric immunoreceptor in order to generate UCB-derived T cells with desired specificity.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy

Serrano

Pfeiffer

Olivares

et al. 2006

Blood

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Disease relapse is a barrier to achieving therapeutic success after unrelated umbilical cord-blood transplantation (UCBT) for B-lineage acute lymphoblastic leukemia (B-ALL). While adoptive transfer of donor-derived tumor-specific T cells is a conceptually attractive approach to eliminating residual disease after allogeneic hematopoietic stem cell transplantation, adoptive immunotherapy after UCBT is constrained by the difficulty of generating antigen-specific T cells from functionally naive umbilical cord-blood (UCB)-derived T cells. Therefore, to generate T cells that recognize B-ALL, we have developed a chimeric immunoreceptor to redirect the specificity of T cells for CD19, a B-lineage antigen, and expressed this transgene in UCB-derived T cells. An ex vivo process, which is compliant with current good manufacturing practice for T-cell trials, has been developed to genetically modify and numerically expand UCB-derived T cells into CD19-specific effector cells. These are capable of CD19-restricted cytokine production and cytolysis in vitro, as well as mediating regression of CD19 ؉ tumor and being selectively eliminated in vivo. Moreover, time-lapse microscopy of the genetically modified T-cell clones revealed an ability to lyse CD19 ؉ tumor cells specifically and repetitively. These data provide the rationale for infusing UCB-derived CD19-specific T cells after UCBT to reduce the incidence of CD19 ؉ B-ALL relapse. IntroductionBanked unrelated umbilical cord blood (UCB) is source of hematopoietic stem cells for patients with B-lineage acute lymphoblastic leukemia (B-ALL). 1 However, despite maximally intensive preparative regimens, disease-relapse remains a significant cause of mortality after umbilical cord-blood transplantation (UCBT).Adoptive therapy after allogeneic hematopoietic stem cell transplantation (HSCT) with ex vivo-expanded donor-derived tumor-specific T cells might be used to augment the graft-versusleukemia (GVL)-effect, thereby reducing the incidence of leukemic relapse, without exacerbating graft-versus-host disease (GVHD). 2,3 While the feasibility of isolating, expanding, and infusing antigen-specific ␣␤ T-cell receptor (TCR) ϩ T cells from peripheral blood (PB) has been validated in animals and humans, 4-10 the naive function of neonatal T cells precludes a priori identification of resident tumor-specific T cells. Redirecting the specificity of T cells through enforced expression of antigenspecific immunoreceptors and differentiating UCB-derived T cells into cytotoxic T lymphocytes (CTLs) is one approach to overcoming this lack of endogenous tumor-specific T cells specific for desired targets. 11,12 We and others are developing adoptive immunotherapy platforms using single-chain chimeric immunoreceptors to redirect the specificity of primary human T cells and NK cells for cell-surface proteins expressed on tumor targets, such as the B-lineage-specific antigen CD19, a molecule expressed on normal and neoplastic B cells. [13][14][15][16][17][18][19][20][21][22] These chimeric immunoreceptor...

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Ex Vivo Expansion of Human Umbilical Cord Blood-Derived T-Lymphocytes with Homologous Cord Blood Plasma

Cited by 16 publications

References 19 publications

Plasma derived from human umbilical cord blood: Potential cell‐additive or cell‐substitute therapeutic for neurodegenerative diseases

Plasma derived from human umbilical cord blood: Potential cell‐additive or cell‐substitute therapeutic for neurodegenerative diseases

Optimization of Culture Conditions to Support Undifferentiated Growth of Human Embryonic Stem Cells

Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy

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