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Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility.

ABSTRACT: Gammadelta (??) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of ?? T cells in umbilical cord blood (UCB) is low, and the majority express ?1, in contrast to blood, whereas the main subset is ?2?9 T cells. UCB ?? T cells are functionally immature, which together with their scarcity complicates the development of UCB ?? T cell therapies. We aimed to develop an effective expansion protocol for UCB ?? T cells based on zoledronate and IL-2. We found that culture with 5??M zoledronate and 200?IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were ?9?2 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal ?? T cell repertoire and the main memory subset was central memory (CD45RO+ CD27+). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of in vitro expanded UCB ?? T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.

SUBMITTER: Berglund S

PROVIDER: S-EPMC5863314 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility.

Berglund Sofia S Gaballa Ahmed A Sawaisorn Piamsiri P Sundberg Berit B Uhlin Michael M

Stem cells international 20180307

Gammadelta (γδ) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of γδ T cells in umbilical cord blood (UCB) is low, and the majority express δ1, in contrast to blood, whereas the main subset is δ2γ9 T cells. UCB γδ T cells are functionally immature, which together with their scarcity complicates the development of UCB γδ T cell therapies. We aimed to develop an effective expansion protocol for UCB γδ ...[more]

PMID: 29707004

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Project description:Uncompromised by chronic disease-related comorbidities, human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDHhi cells) stimulate blood vessel regeneration after intra-muscular transplantation. However, implementation of cellular therapies using UCB ALDHhi cells for critical limb ischemia, the most severe form of severe peripheral artery disease, is limited by the rarity (<0.5%) of these cells. Our goal was to generate a clinically-translatable, allogeneic cell population for vessel regenerative therapies, via ex vivo expansion of UCB ALDHhi cells without loss of pro-angiogenic potency. Purified UCB ALDHhi cells were expanded >18-fold over 6-days under serum-free conditions. Consistent with the concept that ALDH-activity is decreased as progenitor cells differentiate, only 15.1%?±?1.3% of progeny maintained high ALDH-activity after culture. However, compared to fresh UCB cells, expansion increased the total number of ALDHhi cells (2.7-fold), CD34+ /CD133+ cells (2.8-fold), and hematopoietic colony forming cells (7.7-fold). Remarkably, injection of expanded progeny accelerated recovery of perfusion and improved limb usage in immunodeficient mice with femoral artery ligation-induced limb ischemia. At 7 or 28 days post-transplantation, mice transplanted with expanded ALDHhi cells showed augmented endothelial cell proliferation and increased capillary density compared to controls. Expanded cells maintained pro-angiogenic mRNA expression and secreted angiogenesis-associated growth factors, chemokines, and matrix modifying proteins. Coculture with expanded cells augmented human microvascular endothelial cell survival and tubule formation under serum-starved, growth factor-reduced conditions. Expanded UCB-derived ALDHhi cells represent an alternative to autologous bone marrow as an accessible source of pro-angiogenic hematopoietic progenitor cells for the refinement of vascular regeneration-inductive therapies. Stem Cells Translational Medicine 2017;6:1607-1619.

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Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility.

Publications

Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility.

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