Adrenomedullin and endothelin-1 stimulate in vitro expansion of cord blood hematopoietic stem cells.
The improvement of techniques for in vitro expansion of cord blood (CB) hematopoietic stem cells (SCs) is, at present, one main task of tissue engineering. Hence, we investigated whether endothelin-1 (ET-1) and adrenomedullin (AM), two regulatory peptides exerting growth promoting action on several cell systems, favor the in vitro expansion of CB SCs in liquid culture. CB hematopoietic cell middle-term expansion was carried out in a stroma-free liquid culture medium in the presence of ET-1, AM and three different cytokine combinations. After two weeks of incubation, aliquots of expanded-cell suspension were seeded on semisolid medium and clonogenic tests were carried out by counting the number of colony forming units (CFUs) after 14 days of culture. Neither ET-1 nor AM (2.5 x 10(-8) M) were per se able to significantly increase the CFU number, but both peptides magnified the pro-expansive effects of some cytokine cocktails. In light of these findings, we conclude that ET-1 and AM are to be considered novel promising molecules that, in association with cytokines, can be utilized as pro-expansive factors of CB SCs in prevision of their clinical use in allogeneic transplantation.
De Angeli
Sergio
S
Cell Culture Laboratory, Transfusional Center, Treviso Regional Hospital, I-31100 Treviso, Italy.
Del Pup
Laura
L
Febas
Erica
E
Conconi
Maria Teresa
MT
Tommasini
Mara
M
Di Liddo
Rosa
R
Albertin
Giovanna
G
Parnigotto
Pier Paolo
PP
Nussdorfer
Gastone G
GG
D053607:Adrenomedullin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000494:pharmacology*
D016207:Cytokines; D019332:Endothelin-1; D010455:Peptides; D053607:Adrenomedullin