In the human hematopoietic system, rare self-renewing multipotent long-term hematopoietic stem cells (LT-HSCs) are responsible for the lifelong production of mature blood cells and are the rational target for clinical regenerative therapies. However, the heterogeneity in the hematopoietic stem cell compartment and variable outcomes of CRISPR/Cas9 editing make functional interrogation ... More
Ex vivo expanded human cord blood-derived hematopoietic progenitor cells induce lung growth and alveolarization in injured newborn lungs.
AuthorsMao Q,Chu S,Ghanta S,Padbury JF,De Paepe ME
JournalRespiratory research
PubMed ID23522153
BACKGROUND: We investigated the capacity of expanded cord blood-derived CD34+ hematopoietic progenitor cells to undergo respiratory epithelial differentiation ex vivo, and to engraft and attenuate alveolar disruption in injured newborn murine lungs in vivo. METHODS: Respiratory epithelial differentiation was studied in CD34+ cells expanded in the presence of growth factors ... More
Human pluripotent stem cells differentiated in fully defined medium generate hematopoietic CD34- and CD34+ progenitors with distinct characteristics.
AuthorsChicha L,Feki A,Boni A,Irion O,Hovatta O,Jaconi M
JournalPloS one
PubMed ID21364915
BACKGROUND: Differentiation of pluripotent stem cells in vitro provides a powerful means to investigate early developmental fates, including hematopoiesis. In particular, the use of a fully defined medium (FDM) would avoid biases induced by unidentified factors contained in serum, and would also allow key molecular mediators involved in such a ... More
Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures.
AuthorsKennedy M,D'Souza SL,Lynch-Kattman M,Schwantz S,Keller G
JournalBlood
PubMed ID17148580
The onset of hematopoiesis in the mouse embryo and in the embryonic stem (ES) cell differentiation model is defined by the emergence of the hemangioblast, a progenitor with both hematopoietic and vascular potential. While there is evidence for the existence of a hemangioblast in the mouse, it is unclear if ... More
Differentiation of Human-Induced Pluripotent Stem Cells to Macrophages for Disease Modeling and Functional Genomics.
AuthorsShi J,Xue C,Liu W,Zhang H
JournalCurrent protocols in stem cell biology
PubMed ID30537374
Macrophages play important roles in many diseases. We describe a protocol and the associated resources for the differentiation of human induced pluripotent stem cell-derived macrophages (IPSDM) and their applications in understanding human macrophage physiology and relevant diseases. The protocol uses an embryoid bodyâbased approach with a combination of serum-free condition ... More
Tumor RNA transfected DCs derived from iPS cells elicit cytotoxicity against cancer cells induced from colorectal cancer patients in vitro.
Significant efficacy of induced pluripotent stem cells (iPSCs) in generating DCs for cancer vaccine therapy was suggested in our previous studies. In clinical application of DC vaccine therapy, however, few DC vaccine systems have shown strong clinical response. To enhance immunogenicity in the DC vaccine, we transfected patient-derived iPSDCs with ... More
Generation of individualized immunocompatible endothelial cells from HLA-I-matched human pluripotent stem cells.
AuthorsSong C,Wang L,Li Q,Liao B,Qiao W,Li Q,Dong N,Li L
JournalStem cell research & therapy
PubMed ID35109922
BACKGROUND: Endothelial cells (ECs) derived from human-induced pluripotent stem cell (iPSC) are a valuable cell resource for cardiovascular regeneration. To avoid time-consuming preparation from primary autologous cells, the allogeneic iPSC-ECs are being expected to become âoff-the-shelfâ cell products. However, allorejection caused by HLA mismatching is a major barrier for this ... More
Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.
AuthorsArdehali R, Ali SR, Inlay MA, Abilez OJ, Chen MQ, Blauwkamp TA, Yazawa M, Gong Y, Nusse R, Drukker M, Weissman IL,
JournalProc Natl Acad Sci U S A
PubMed ID23391730
'A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity ... More
Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm.
AuthorsWillems E, Spiering S, Davidovics H, Lanier M, Xia Z, Dawson M, Cashman J, Mercola M,
JournalCirc Res
PubMed ID21737789
'Human embryonic stem cells can form cardiomyocytes when cultured under differentiation conditions. Although the initiating step of mesoderm formation is well characterized, the subsequent steps that promote for cardiac lineages are poorly understood and limit the yield of cardiomyocytes. Our aim was to develop a human embryonic stem cell-based high-content ... More
Directed differentiation and mass cultivation of pure erythroid progenitors from mouse embryonic stem cells.
AuthorsCarotta S, Pilat S, Mairhofer A, Schmidt U, Dolznig H, Steinlein P, Beug H,
JournalBlood
PubMed ID15166028
Differentiating embryonic stem (ES) cells are an increasingly important source of hematopoietic progenitors, useful for both basic research and clinical applications. Besides their characterization in colony assays, protocols exist for the cultivation of lymphoid, myeloid, and erythroid cells. With the possible exception of mast cells, however, long-term expansion of pure ... More
LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo.
AuthorsLee YT, de Vasconcellos JF, Yuan J, Byrnes C, Noh SJ, Meier ER, Kim KS, Rabel A, Kaushal M, Muljo SA, Miller JL,
Journal
PubMed ID23798711
Reactivation of fetal hemoglobin (HbF) holds therapeutic potential for sickle cell disease and ß-thalassemias. In human erythroid cells and hematopoietic organs, LIN28B and its targeted let-7 microRNA family, demonstrate regulated expression during the fetal-to-adult developmental transition. To explore the effects of LIN28B in human erythroid cell development, lentiviral transduction was ... More
A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability.
AuthorsBurridge PW, Thompson S, Millrod MA, Weinberg S, Yuan X, Peters A, Mahairaki V, Koliatsos VE, Tung L, Zambidis ET,
JournalPLoS One
PubMed ID21494607
The production of cardiomyocytes from human induced pluripotent stem cells (hiPSC) holds great promise for patient-specific cardiotoxicity drug testing, disease modeling, and cardiac regeneration. However, existing protocols for the differentiation of hiPSC to the cardiac lineage are inefficient and highly variable. We describe a highly efficient system for differentiation of ... More
An optimized protocol for the generation and functional analysis of human mast cells from CD34(+) enriched cell populations.
AuthorsYin Y, Bai Y, Olivera A, Desai A, Metcalfe DD
JournalJ Immunol Methods
PubMed ID28629733
'The culture of mast cells from human tissues such a cord blood, peripheral blood or bone marrow aspirates has advanced our understanding of human mast cells (huMC) degranulation, mediator production and response to pharmacologic agents. However, existing methods for huMC culture tend to be laborious and expensive. Combining technical approaches ... More
Influence of IL-3 functional fragment on cord blood stem cell ex vivo expansion and differentiation.
AuthorsRen Z, Zhang Y, Zhang Y, Jiang W, Dai W, Ding X, Jiang Y,
JournalStem Cell Investig
PubMed ID27358898
'Recombinant human interleukin-3 (rhIL-3) is a multiple hematopoietic growth factor, which enhances stem cell expansion and hematopoiesis regeneration in vitro and in vivo, when administrated in combination with other cytokines. However, the structure-function study of rhIL-3 remains rarely studied, so far. The purpose of this study was to recognize the ... More
Directed Differentiation of Human Pluripotent Stem Cells to Microglia.
AuthorsDouvaras P, Sun B, Wang M, Kruglikov I, Lallos G, Zimmer M, Terrenoire C, Zhang B, Gandy S, Schadt E, Freytes DO, Noggle S, Fossati V
JournalStem Cell Reports
PubMed ID28528700
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. ... More
Generation and characterization of human iPSC line from CD34(+) cells isolated from umbilical cord blood belonging to Indian origin.
AuthorsFernandes S, Talwadekar M, Agarwal R, Nair V, Kale V, Limaye L
JournalStem Cell Res
PubMed ID28395807
We describe here the reprogramming of CD34(+) cells isolated from umbilical cord blood obtained after full term delivery of a healthy female child of Indian origin. The cells were nucleofected by episomal vectors expressing Oct4, Sox2, L-Myc, Klf4, Lin28 and p53DD (negative mutation in p53). Colonies were identified by alkaline ... More
Haematopoietic stem and progenitor cells from human pluripotent stem cells.
AuthorsSugimura R, Jha DK, Han A, Soria-Valles C, da Rocha EL, Lu YF, Goettel JA, Serrao E, Rowe RG, Malleshaiah M, Wong I, Sousa P, Zhu TN, Ditadi A, Keller G, Engelman AN, Snapper SB, Doulatov S, Daley GQ
JournalNature
PubMed ID28514439
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation ... More