Functional Assessment of Hematopoietic Niche Cells Derived from Human Embryonic Stem Cells

Ferrell, Patrick I.; Hexum, Melinda K.; Kopher, Ross A.; Lepley, Michael; Gussiaas, Amanda; Kaufman, Dan S.

doi:10.1089/scd.2013.0497

Cited by 7 publications

(7 citation statements)

References 41 publications

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“…26 Human umbilical cord blood (hUCB) samples were obtained from the University of Colorado Cord Blood Bank, ClinImmune Stem Cell Laboratory. 29…”

Section: Methodsmentioning

confidence: 99%

“…M2-10B4 murine bone marrow stromal cells were purchased from the ATCC (Manassas, VA, USA) and maintained following established protocols (57). Samples of human umbilical cord blood (hUCB) were obtained from the ClinImmune Stem Cell Laboratory at the University of Colorado Cord Blood Bank (60).…”

Section: Methodsmentioning

confidence: 99%

“…M2-10B4 murine bone marrow stromal cells were purchased from the ATCC (Manassas, VA, USA) and maintained as previously described [25]. Human umbilical cord blood (hUCB) samples were obtained from the University of Colorado Cord Blood Bank, ClinImmune Stem Cell Laboratory [28].…”

Section: Human and Mouse Cell Linesmentioning

confidence: 99%

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Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion

Kim

Schulte

Sarver

et al. 2021

Preprint

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Hemangiosarcoma and angiosarcoma are soft tissue sarcomas of malignant blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs that support the niche, enabling progression of canine hemangiosarcoma and human angiosarcoma. Here, we show that the transcriptional landscape of canine hemangiosarcoma and human angiosarcoma included comparable angiogenic and inflammatory programs. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells, a trait that was not observed in xenografts from canine osteosarcoma and lymphoma. In some cases, the xenografted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. We did not uncover a definitive transmissible etiology, but our data indicate that transcriptional programs of hemangiosarcoma cells resemble those of hematopoietic nurse cells, and these malignant cells support expansion and differentiation of human hematopoietic progenitors. We conclude that canine hemangiosarcoma, and possibly human angiosarcoma, originate from nurse cells that make up the stromal bone marrow niche, and that these cells may also support the growth of hematopoietic tumors.

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“…26 Human umbilical cord blood (hUCB) samples were obtained from the University of Colorado Cord Blood Bank, ClinImmune Stem Cell Laboratory. 29…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion

Kim

Schulte

Sarver

et al. 2021

Preprint

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“…We and others have shown that mesenchymal cells can be differentiated from human pluripotent stem cells (hPSCs) ( Chin et al., 2016 , Ferrell et al., 2014 , Hoffman and Calvi, 2014 , Vodyanik et al., 2010 ). These previous studies identified mesenchyme as a single population defined mostly by expression of CD73 and/or CD105 and absence of hematopoietic and endothelial markers.…”

Section: Introductionmentioning

confidence: 99%

Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells

Chin

Corselli

et al. 2018

Stem Cell Reports

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SummaryVarious mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSCs), the capacity of such cells to support hematopoiesis has not been reported. Here, we demonstrate that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, and PDGFRβ), a subset of cells defined as CD146hiCD73hi expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146loCD73lo cells supported differentiation. Stromal support of HSPCs was contact dependent and mediated in part through high JAG1 expression and low WNT signaling. Molecular profiling revealed significant transcriptional similarity between hPSC-derived CD146++ and primary human CD146++ perivascular cells. The derivation of functionally diverse types of mesenchyme from hPSCs opens potential avenues to model the HSPC niche and develop PSC-based therapies.

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“…OP9 is typically used as a support for the differentiation of CD34 + cells from embryonic stem cells (ESCs) or pluripotent stem cells ( 18 – 21 ). Instead, M2-10B4 is a good support to maintain CD34 + cells in a long-term culture, acting like a hematopoietic niche ( 22 ). Our data show that these two culture conditions generated a large number of mature and functional NK cells.…”

Section: Introductionmentioning

confidence: 99%

OP9 Feeder Cells Are Superior to M2-10B4 Cells for the Generation of Mature and Functional Natural Killer Cells from Umbilical Cord Hematopoietic Progenitors

Herrera¹,

Salcedo²,

Santos³

et al. 2017

Front. Immunol.

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Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of mature and functional NK cells. An option for future immunotherapy treatments is to use large amounts of NK cells derived and differentiated from umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), mainly because UCB is one of the most accessible HSC sources. In our study, we compared the potential of two stromal cell lines, OP9 and M2-10B4, for in vitro generation of mature and functional CD56+ NK cells from UCB CD34+ HSC. We generated higher number of CD56+ NK cells in the presence of the OP9 cell line than when they were generated in the presence of M2-10B4 cells. Furthermore, higher frequency of CD56+ NK cells was achieved earlier when cultures were performed with the OP9 cells than with the M2-10B4 cells. Additionally, we studied in detail the maturation stages of CD56+ NK cells during the in vitro differentiation process. Our data show that by using both stromal cell lines, CD34+ HSC in vitro differentiated into the terminal stages 4–5 of maturation resembled the in vivo differentiation pattern of human NK cells. Higher frequencies of more mature NK cells were reached earlier by using OP9 cell line than M2-10B4 cells. Alternatively, we observed that our in vitro NK cells expressed similar levels of granzyme B and perforin, and there were no significant differences between cultures performed in the presence of OP9 cell line or M2-10B4 cell line. Likewise, degranulation and cytotoxic activity against K562 target cells were very similar in both culture conditions. The results presented here provide an optimal strategy to generate high numbers of mature and functional NK cells in vitro, and point toward the use of the OP9 stromal cell line to accelerate the culture procedure to obtain them. Furthermore, this method could establish the basis for the generation of mature NK cells ready for cancer immunotherapy.

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Functional Assessment of Hematopoietic Niche Cells Derived from Human Embryonic Stem Cells

Cited by 7 publications

References 41 publications

Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion

Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion

Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells

OP9 Feeder Cells Are Superior to M2-10B4 Cells for the Generation of Mature and Functional Natural Killer Cells from Umbilical Cord Hematopoietic Progenitors

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