Study of Cell Dose and Storage Time on Engraftment of Cryopreserved Autologous Bone Marrow in a Canine Model

Appelbaum, F; Herzig, Geoffrey P.; Graw, Robert G.; Bull, MI; Bowles, Charles A.; Gorin, NC; Deisseroth, AB

doi:10.1097/00007890-197810000-00008

Cited by 63 publications

(29 citation statements)

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“…Granulocytes reconstituted in the surviving animals on days 30 and 26 and platelets on days 31 and 26. Similar cell-dose and time-to-engraftment data have been reported in canine marrow transplantation studies [23,24].…”

Section: Very Low Density (<1050 G/ml) Feline Marrow Cells Contain Hsupporting

confidence: 79%

The Ex Vivo Expansion of Feline Marrow Cells Leads to Increased Numbers of BFU‐E and CFU‐GM but a Loss of Reconstituting Ability

et al. 1998

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Some studies in mice suggest that hematopoietic stem cells can be maintained and possibly expanded ex vivo. As there is a paucity of data from larger animals, we have studied hematologic reconstitution following autologous marrow transplantation in cats. Transplantation of very low density marrow cells (<1.050 g/ml), termed "1050 cells," at 2 × 10 5 cells/kg leads to rapid hematopoietic recovery (granulocytes >200/µl by day 20 ± 2 and platelets >50 × 10 3 /µl by day 21 ± 3). Recovery rates are comparable when 1-2 × 10 7 nucleated marrow cells/kg are infused, suggesting that reconstituting cells are enriched 50-to 100-fold in the 1050 cell preparation. To explore if the numbers of reconstituting cells could be expanded ex vivo, 1050 cells were cultured in the presence of 5 ng/ml recombinant human interleukin 1β, 10 ng/ml recombinant canine (rc)G-CSF, 2 U/ml rHu erythropoietin, and 5 ng/ml rc stem cell factor. Maximum numbers of BFU-E and colony-forming units-granulocyte/macrophage (CFU-GM) were generated at day 6. However, when 10 6 1050 cells/kg (5× that needed for hematologic recovery) were cultured for six days and all resulting cells infused into irradiated donor animals, two of nine (22%) engrafted. Even when flt3 ligand (100 ng/ml) was added to cultures, only two of five animals (40%) engrafted (p = NS versus studies without flt3 ligand). These data confirm that BFU-E and CFU-GM provide inaccurate estimates of reconstituting cells and demonstrate that the number or function of feline reconstituting cells is impaired by in vitro culture with cytokines.

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Section: Very Low Density (<1050 G/ml) Feline Marrow Cells Contain Hsupporting

confidence: 79%

The Ex Vivo Expansion of Feline Marrow Cells Leads to Increased Numbers of BFU‐E and CFU‐GM but a Loss of Reconstituting Ability

et al. 1998

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“…They did not directly compare the original and current results for each individual specimen, but the data indicated that the stem cells stored the longest had the lowest CD34 þ cell counts and CFU-GM. Other studies have also shown a decrease in CFU-GM or engraftment with long-term storage but are less applicable because of the use of less extreme freezing temperatures 17 or the use of animal models 18 and studies that report no decrease in SCP markers have been limited by relatively short median storage times. [9][10][11][12]19 In this study, recovery of SCP, TNC, cell viability and total CD34 þ cell count decreased as storage time, up to 19 years, increased.…”

Section: Discussionmentioning

confidence: 99%

Relative recovery of haematopoietic stem cell products after cryogenic storage of up to 19 years

Fernyhough

Buchan

McArthur

et al. 2012

Bone Marrow Transplant

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There is an increasing trend towards long-term frozen storage of haematopoietic stem cells. For such stem cells, harvested from peripheral blood (PB) or BM, it is not known if stem cell viability decreases with time. In this study, 31 separate bags of stem cell product (SCP) stored for 11-19 years (median 15 years) were assessed for total nucleated cell (TNC) count, colony forming unitgranulocyte/macrophage (CFU-GM), CD34 þ cell count and cell viability. The results were compared with the initial results obtained for the products at the time of stem cell harvest, and the percentage recovery of each parameter was plotted against time. Recovery of TNC, CD34 þ cell count and cell viability decreased with time (P ¼ o0.01) but CFU-GM did not. This study shows that SCPs harvested from PB and BM do deteriorate with long-term storage. This could have an impact on rates of engraftment.

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“…The details of this model with respect to animal selection, care, irradiation, postirradiation supportive care, and criteria for engraftment have been described (16,17). The model utilizes a hematopoietically lethal dose of total body irradiation (TBI) (900 rad midplane dose at 9 rad/min) followed by supportive care with parenteral fluids, antibiotics, and platelets.…”

Section: Methodsmentioning

confidence: 99%

“…Following collection, cells were cryopreserved in 10% dimethyl sulfoxide as described (16,17), and the frozen preparations were immersed in liquid nitrogen (-196°C) until needed for reinfusion. Time from cell collection to cell infusion (following TBI) averaged 7 wk.…”

Section: Methodsmentioning

confidence: 99%

Cyclophosphamide treatment expands the circulating hematopoietic stem cell pool in dogs.

Abrams¹,

McCormack²,

Bowles³

et al. 1981

J. Clin. Invest.

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Study of Cell Dose and Storage Time on Engraftment of Cryopreserved Autologous Bone Marrow in a Canine Model

Cited by 63 publications

References 0 publications

The Ex Vivo Expansion of Feline Marrow Cells Leads to Increased Numbers of BFU‐E and CFU‐GM but a Loss of Reconstituting Ability

The Ex Vivo Expansion of Feline Marrow Cells Leads to Increased Numbers of BFU‐E and CFU‐GM but a Loss of Reconstituting Ability

Relative recovery of haematopoietic stem cell products after cryogenic storage of up to 19 years

Cyclophosphamide treatment expands the circulating hematopoietic stem cell pool in dogs.

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