Quantitative Analysis Demonstrates Expansion of SCID‐Repopulating Cells and Increased Engraftment Capacity in Human Cord Blood Following Ex Vivo Culture with Human Brain Endothelial Cells

Abstract

ABSTRACT

Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice

“…[7][8][9] Our laboratory has shown that primary human brain-derived endothelial cells produce a soluble hematopoietic activity that supports a 1 to 2 log expansion of the most primitive assayable human hematopoietic cell, which is capable of long-term repopulation in nonobese diabetic/severe combined immunodeficient mice. [10][11][12] Li et al 13 have also confirmed that murine brain-and heart-derived endothelial cells can support the maintenance of colony-forming unit-spleen day-8 colonies in vitro. Taken together, these data implicate vascular endothelial cells as a source of proliferative and regenerative signals for hematopoietic stem and progenitor cells.…”

“…Although these studies have demonstrated the capacity of endothelial cells to support hematopoiesis in vitro, [7][8][9][10][11][12][13] evidence of the in vivo contribution of endothelial cells to adult hematopoiesis has begun to emerge. Blockade of N-cadherin on vascular endothelial cells in the BM has been associated with delayed megakaryocyte recovery in 5-FUtreated mice, 5 and accelerated repair of this BM vascular niche has been associated with early megakaryocytopoiesis after chemotherapy.…”

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

“…63 It is currently not known whether non-contact conditions are sufficient for ex vivo expansion or whether stromal binding is required. 64 MSCs have been used in preclinical models as a method to maintain stem cells in an immature state. MSCs give rise to osteoblasts, chondrocytes, adipocytes and myelosupportive stroma.…”

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?

“…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.…”