MAPC culture conditions support the derivation of cells with nascent hypoblast features from bone marrow and blastocysts

Nigro, Antonio Lo; Geraerts, Martine; Notelaers, Tineke; Roobrouck, Valerie D.; Muijtjens, Manja; Eggermont, Kristel; Subramanian, Kartik; Ulloa‐Montoya, Fernando; Park, Yonsil; Owens, Jason; Burns, Terry C.; Low, Walter C.; Sharma, Shikha; Sohni, Abhishek; Crabbe, Annelies; Pauwelyn, Karen; Roelandt, Philip; Agirre, Xabier; Prósper, Felipe; O’Brien, Timothy; Zwijsen, An; Hu, Wei Shou; Binas, Bert; Verfaillie, Catherine M.

doi:10.1093/jmcb/mjs046

Cited by 19 publications

(35 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As rHypoSC have a similar gene expression profile and differentiation ability in vitro compared with rMAPC [25], we tested if the protocol used for rMAPC would also induce commitment of blastocyst-derived rHypoSC towards pancreatic endoderm and β-cell like cells in vitro . Studies were done using two independently derived cell lines, Fi2 and WK8.…”

Section: Resultsmentioning

confidence: 99%

“…After 2–10 cells, cells with refractile morphology appeared, which could be expanded into cell lines by passaging on fibronectin-coated 100-mm dishes in rMAPC expansion medium. The rHyPoSc lines Fi2 and Wk8 were used in this study [25].…”

Section: Methodsmentioning

confidence: 99%

“…This formed the basis for studies described here wherein we tested if these cells can also be specified to insulin-secreting β-cells. Aside from evaluating rMAPC, we also evaluated the differentiation potential of rat extra-embryonic progenitor cells (rXEN-P) [24], isolated directly from rat blastocysts using rMAPC culture conditions (termed hypoblast stem cells or rHypoSC) [25]. Like rMAPC [25], [26], rHypoSC are a homogenous population of SSEA1/CD31-positive cells that express aside from Oct4 also a number of nascent hypoblast genes including FoxA2, Gata binding protein (Gata)6, Gata4, and Hnf1β, but not Nanog or Sox2, typical for ESC, caudal type homeobox 2 (Cdx2), typical for trophoblast or Hnf4α and αFetoprotein (αFP), typical for primitive endoderm (PrE).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

β-cell replacement may efficiently cure type 1 diabetic (T1D) patients whose insulin-secreting β-cells have been selectively destroyed by autoantigen-reactive T cells. To generate insulin-secreting cells we used two cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly similar rat extra-embryonic endoderm precursor (rXEN-P) cells isolated under rMAPC conditions from blastocysts (rHypoSC). rMAPC/rHypoSC were sequentially committed to definitive endoderm, pancreatic endoderm, and β-cell like cells. On day 21, 20% of rMAPC/rHypoSC progeny expressed Pdx1 and C-peptide. rMAPCr/HypoSC progeny secreted C-peptide under the stimulus of insulin agonist carbachol, and was inhibited by the L-type voltage-dependent calcium channel blocker nifedipine. When rMAPC or rHypoSC differentiated d21 progeny were grafted under the kidney capsule of streptozotocin-induced diabetic nude mice, hyperglycemia reversed after 4 weeks in 6/10 rMAPC- and 5/10 rHypoSC-transplanted mice. Hyperglycemia recurred within 24 hours of graft removal and the histological analysis of the retrieved grafts revealed presence of Pdx1-, Nkx6.1- and C-peptide-positive cells. The ability of both rMAPC and HypoSC to differentiate to functional β-cell like cells may serve to gain insight into signals that govern β-cell differentiation and aid in developing culture systems to commit other (pluripotent) stem cells to clinically useful β-cells for cell therapy of T1D.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, in some cases, tumor formation may be context dependent. Although no tumors were found with system or intramuscular cell delivery (Aranguren et al, 2008;Serafini et al, 2007), the same cells generated embryonic yolk sac tumors in nude mice (Leten et al, 2014;Lo Nigro et al, 2012) and after intracranial delivery. As such, there remains no substitute for rigorous long-term safety studies in animals, to evaluate the behavior of cells delivered at or above the passage number and density planned for clinical trials.…”

Section: Primum Non Nocerementioning

confidence: 91%

“…Great efforts have been invested in culture, sorting and screening strategies to ensure "pure" populations ESC-derived cells safe for clinical use (Lukovic et al, 2014;Polanco et al, 2013). Third, certain in vitro culture conditions have recently been found to enable spontaneous de-differentiation of bone marrowderived cells into hypoblast cells that can generate embryonic yolk sac tumors, even though cells may be derived from bone marrow and have normal Karyotype (Leten et al, 2014;Lo Nigro et al, 2012). As such, even cell types presumed to be "safe" based on their adult origin, lack of genetic manipulation and normal karyotype, must be rigorously evaluated for markers of dedifferentiation such as Oct4.…”

Section: Primum Non Nocerementioning

confidence: 99%

From mice to mind: Strategies and progress in translating neuroregeneration

Burns

Verfaillie

2015

European Journal of Pharmacology

Self Cite

View full text Add to dashboard Cite

Decisions about what experimental therapies are advanced to clinical trials are based almost exclusively on findings in preclinical animal studies. Over the past 30 years, animal models have forecast the success of hundreds of neuroprotective pharmacological therapies for stroke, Alzheimer׳s disease, spinal cord injury, traumatic brain injury and amyotrophic lateral sclerosis. Yet almost without exception, all have failed. Rapid advances in stem cell technologies have raised new hopes that these neurological diseases may one day be treatable. Still, how can neuroregenerative therapies be translated into clinical realities if available animal models are such poor surrogates of human disease? To address this question we discuss human and rodent neurogenesis, evaluate mechanisms of action for cellular therapies and describe progress in translating neuroregeneration to date. We conclude that not only are appropriate animal models critical to the development of safe and effective therapies, but that the multiple mechanisms of stem cell-mediated therapies may be particularly well suited to the mechanistically diverse nature of central nervous system diseases in mice and man.

show abstract

Concise Review: Bone Marrow Meets Blastocyst: Lessons from an Unlikely Encounter

Binas

Verfaillie

2013

Stem Cells

Self Cite

View full text Add to dashboard Cite

This article discusses the implications of the recent discovery that rat bone marrow-derived multipotent adult progenitor cells (rMAPCs), a cell type with broad somatic differentiation potential but of uncertain lineage identity, are similar to rat blastocystderived extraembryonic endoderm precursor (rXENP) cells, which appear to represent the committed extraembryonic endoderm precursor of the blastocyst. It was found that under rMAPC culture conditions, rXENP cells can be homogeneously cultured and similar cells, named rat hypoblast stem cells (rHypoSCs), can be derived from rat blastocysts more rapidly and directly. The detailed comparison of rHypoSCs, rXENP cells, and rMAPCs revealed highly similar gene expression profiles and developmental potentials. The significance of these findings for embryology, stem cell biology, and medicine is discussed. Specifically, the results assign a lineage identity to rMAPCs, indicate that rMAPCs originated by environmental reprogramming, and imply that HypoSCs, XENP cells, and MAPCs possess lineage plasticity. The MAPC-HypoSC relation also strengthens the consistency of rat and mouse embryology and consequently the idea that HypoSCs represent the committed extraembryonic endoderm precursor of the blastocyst. On this basis, it is argued that the direct comparison of HypoSCs (now available in pure form) with embryonic stem cells will be highly useful for the understanding of pluripotency and plasticity. Finally, the new findings suggest an explanation for an obscure observation on stem cell-induced transplantation tolerance. Thus, the HypoSC/ XENP/MAPC phenotype provides a unique but broadly instructive model with which to study stem cell plasticity, reprogramming, and transplantation tolerance, all central themes in regenerative medicine. STEM CELLS 2013;31:620-626

show abstract

MAPC culture conditions support the derivation of cells with nascent hypoblast features from bone marrow and blastocysts

Cited by 19 publications

References 14 publications

Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells

Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells

From mice to mind: Strategies and progress in translating neuroregeneration

Concise Review: Bone Marrow Meets Blastocyst: Lessons from an Unlikely Encounter

Contact Info

Product

Resources

About