Generation of a transplantable erythropoietin-producer derived from human mesenchymal stem cells.
Differentiation of autologous stem cells into functional transplantable tissue for organ regeneration is a promising regenerative therapeutic approach for cancer, diabetes, and many human diseases. Yet to be established, however, is differentiation into tissue capable of producing erythropoietin (EPO), which has a critical function in anemia. We report a novel EPO-producing organ-like structure (organoid) derived from human mesenchymal stem cells. Using our previously established relay culture system, a human mesenchymal stem cell-derived, human EPO-competent organoid was established in rat omentum. The organoid-derived levels of human EPO increased in response to anemia induced by rapid blood withdrawal. In addition, the presence of an organoid in rats suppressed for native (rat) EPO production enhanced recovery from anemia when compared with control animals lacking the organoid. Together these results confirmed the generation of a stem cell-derived organoid that is capable of producing EPO and sensitive to physiological regulation.
Yokoo
Takashi
T
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. tyokoo@jikei.ac.jp
Fukui
Akira
A
Matsumoto
Kei
K
Ohashi
Toya
T
Sado
Yoshikazu
Y
Suzuki
Hideaki
H
Kawamura
Tetsuya
T
Okabe
Masataka
M
Hosoya
Tatsuo
T
Kobayashi
Eiji
E
D000818:Animals; D004921:Erythropoietin / Q000096:biosynthesis*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D016377:Organ Transplantation / Q000502:physiology*; D009940:Organoids / Q000378:metabolism*
D004921:Erythropoietin; C100266:erythrogenin