PMID- 19937912 OWN - NLM STAT- MEDLINE DCOM- 20100811 LR - 20181201 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 4 IP - 2 DP - 2010 Feb TI - Dynamic cell-cell interactions between cord blood haematopoietic progenitors and the cellular niche are essential for the expansion of CD34+, CD34+CD38- and early lymphoid CD7+ cells. PG - 149-58 LID - 10.1002/term.226 [doi] AB - Most clinical applications of haematopoietic stem/progenitor cells (HSCs) would benefit from their ex vivo expansion to obtain a therapeutically significant amount of cells from the available donor samples. We studied the impact of cellular interactions between umbilical cord blood (UCB) haematopoietic cells and bone marrow (BM)-derived mesenchymal stem cells (MSCs) on the ex vivo expansion and differentiative potential of UCB CD34(+)-enriched cells. UCB cells were cultured: (a) directly in contact with BM MSC-derived stromal layers (contact); (b) separated by a microporous membrane (non-contact); or (c) without stroma (no stroma). Highly dynamic culture events occurred in HSC-MSC co-cultures, involving cell-cell interactions, which preceded HSC expansion. Throughout the time in culture [18 days], total cell expansion was significantly higher in contact (fold increase of 280 + or - 37 at day 18) compared to non-contact (85 + or - 25). No significant cell expansion was observed in stroma-free cultures. CD34(+) cell expansion was also clearly favoured by direct contact with BM MSCs (35 + or - 5- and 7 + or - 3-fold increases at day 18 for contact and non-contact, respectively). Moreover, a higher percentage of CD34(+)CD38(-) cells was consistently maintained during the time in culture under contact (8.1 + or - 1.9% at day 18) compared to non-contact (5.7 + or - 1.6%). Importantly, direct cell interaction with BM MSCs significantly enhanced the expansion of early lymphoid CD7(+) cells, yielding considerably higher (x3-10) progenitor numbers compared to non-contact conditions. These results highlight the importance of dynamic cell-cell interactions between UCB HSCs and BM MSCs, towards the maximization of HSC expansion ex vivo to obtain clinically relevant cell numbers for multiple settings, such as BM transplantation or somatic cell gene therapy. FAU - da Silva, Claudia Lobato AU - da Silva CL AD - IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Tecnico, Avenida Rovisco Pais, 1049-001 Lisbon, Portugal. claudia lobato@ist.utl.pt FAU - Goncalves, Raquel AU - Goncalves R FAU - dos Santos, Francisco AU - dos Santos F FAU - Andrade, Pedro Z AU - Andrade PZ FAU - Almeida-Porada, Graca AU - Almeida-Porada G FAU - Cabral, Joaquim M S AU - Cabral JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Antigens, CD34) RN - 0 (Antigens, CD7) RN - 0 (Suspensions) RN - EC 3.2.2.6 (ADP-ribosyl Cyclase 1) SB - IM MH - ADP-ribosyl Cyclase 1/*metabolism MH - Antigens, CD34/*metabolism MH - Antigens, CD7/*metabolism MH - Cell Adhesion MH - *Cell Communication MH - Cell Differentiation MH - Cell Proliferation MH - Cells, Cultured MH - Coculture Techniques MH - Colony-Forming Units Assay MH - Fetal Blood/*cytology MH - Flow Cytometry MH - Hematopoietic Stem Cells/*cytology/metabolism MH - Humans MH - Lymphocytes/cytology/metabolism MH - Mesenchymal Stem Cells/cytology/metabolism MH - Microscopy, Electron, Scanning MH - Phenotype MH - Stem Cell Niche/*cytology MH - Suspensions EDAT- 2009/11/26 06:00 MHDA- 2010/08/12 06:00 CRDT- 2009/11/26 06:00 PHST- 2009/11/26 06:00 [entrez] PHST- 2009/11/26 06:00 [pubmed] PHST- 2010/08/12 06:00 [medline] AID - 10.1002/term.226 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2010 Feb;4(2):149-58. doi: 10.1002/term.226.