Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use.
We report a phase I trial to determine the feasibility of collection, ex vivo culture-expansion and intravneous infusion of human bone marrow-derived progenitor stromal cells (mesenchymal progenitor cells (MPCs)). Ten milliliter bone marrow samples were obtained from 23 patients with hematologic malignancies in complete remission. Bone marrow mononuclear cells were separated and adherent cells were culture-expanded in vitro for 4-7 weeks. Autologous MPCs were reinfused intravenously and a bone marrow examination repeated 2 weeks later for histologic assessment and in vitro hematopoietic cultures. Patient age ranged from 18 to 68 years and 12 subjects previously had undergone an autologous or syngeneic bone marrow transplant 4-52 months prior to collection of MPCs. A median of 364 x 10(6) nucleated bone marrow cells (range: 103 to 1004 x 10(6)) were used for ex vivo expansion. Median number of MPCs which were obtained after ex vivo culture expansion was 59.0 (range: 1.1 to 347 x 10(6)) representing a median cell doubling of 16,000-fold (13 doublings). Fifteen of 23 patients completed the ex vivo expansion and underwent MPC infusion. Time to infusion of MPCs after collection ranged from 28 to 49 days. Five patients in each of three groups were given 1, 10 and 50 x 10(6) MPCs. No adverse reactions were observed with the infusion of the MPCs. MPCs obtained from cancer patients can be collected, expanded in vitro and infused intravenously without toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Lazarus
H M
HM
Department of Medicine, Ireland Cancer Center of University Hospitals of Cleveland, Case Western Reserve University, Ohio 44106, USA.
Haynesworth
S E
SE
Gerson
S L
SL
Rosenthal
N S
NS
Caplan
A I
AI
D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017154:Stromal Cells