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

Binas, Bert; Verfaillie, Catherine M.

doi:10.1002/stem.1287

Cited by 8 publications

(5 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although further studies will be necessary to identify the mode of action and active components involved in MIN6 NV-mediated BM cell differentiation, our in vitro data suggested that the insulin-producing cells that were differentiated in vivo may have been derived from certain lineage-negative BM cells. Because cellular plasticity phenomena are remarkable and are involved in many more cell types than originally thought, , the contributions of different cell populations, including lineage-positive cells, require further investigation. Nonetheless, the usage of naïve whole BM cells has additional benefits over the use of cultured (pluripotent) cells, which have tumorigenic potential. , …”

Section: Resultsmentioning

confidence: 99%

In Vivo Differentiation of Therapeutic Insulin-Producing Cells from Bone Marrow Cells via Extracellular Vesicle-Mimetic Nanovesicles

Kim

et al. 2015

ACS Nano

View full text Add to dashboard Cite

The current diabetes mellitus pandemic constitutes an important global health problem. Reductions in the mass and function of β-cells contribute to most of the pathophysiology underlying diabetes. Thus, physiological control of blood glucose levels can be adequately restored by replacing functioning β-cell mass. Sources of functional islets for transplantation are limited, resulting in great interest in the development of alternate sources, and recent progress regarding cell fate change via utilization of extracellular vesicles, also known as exosomes and microvesicles, is notable. Thus, this study investigated the therapeutic capacity of extracellular vesicle-mimetic nanovesicles (NVs) derived from a murine pancreatic β-cell line. To differentiate insulin-producing cells effectively, a three-dimensional in vivo microenvironment was constructed in which extracellular vesicle-mimetic NVs were applied to subcutaneous Matrigel platforms containing bone marrow (BM) cells in diabetic immunocompromised mice. Long-term control of glucose levels was achieved over 60 days, and differentiation of donor BM cells into insulin-producing cells in the subcutaneous Matrigel platforms, which were composed of islet-like cell clusters with extensive capillary networks, was confirmed along with the expression of key pancreatic β-cell markers. The resectioning of the subcutaneous Matrigel platforms caused a rebound in blood glucose levels and confirmed the source of functioning β-cells. Thus, efficient differentiation of therapeutic insulin-producing cells was attained in vivo through the use of extracellular vesicle-mimetic NVs, which maintained physiological glucose levels.

show abstract

Section: Resultsmentioning

confidence: 99%

In Vivo Differentiation of Therapeutic Insulin-Producing Cells from Bone Marrow Cells via Extracellular Vesicle-Mimetic Nanovesicles

Kim

et al. 2015

ACS Nano

View full text Add to dashboard Cite

show abstract

“…These data suggest that murine bone marrow cells do not transdifferentiate into cell types of diverse lineages, but inherently contain more diverse and primitive stem cell populations that could develop into conventional three germ layer components depending on their in vitro or in vivo microenvironment. 30 Our protocol for differentiation of functioning hepatocytes from bone marrow cells is unusually simple and efficient. Moreover, similar to pluripotent stem cell differentiation protocols, we successfully reiterated the various normal-like sequential developmental stages, which guarantee more physiologically relevant cells.…”

Section: Discussionmentioning

confidence: 99%

Murine Sca1+Lin− bone marrow contains an endodermal precursor population that differentiates into hepatocytes

Shon

Seo

et al. 2015

Exp Mol Med

View full text Add to dashboard Cite

The direct differentiation of hepatocytes from bone marrow cells remains controversial. Several mechanisms, including transdifferentiation and cell fusion, have been proposed for this phenomenon, although direct visualization of the process and the underlying mechanisms have not been reported. In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1+ subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which indicates that lineage-negative bone marrow cells contain more diverse multipotent stem cells than considered previously. The presence of equivalent endodermal precursor populations in human bone marrow would facilitate the development of these cells into an effective treatment modality for chronic liver diseases.

show abstract

“…It is also interesting to point out here that OCT-4 is one of the sensitive markers increasingly being used for diagnosis of carcinoma in situ in germ cell tumors [25,26]. Several groups have suggested that [27,28], these VSELs may be the similar to the MAPCs described by Verfaillie's group [29]. Many groups have reported successful derivation of ES-like colonies from testicular tissue culture in mice [30] as well as in humans [31,32] and proposed the origin of the colonies to be dedifferentiation of SSCs.…”

Section: Introductionmentioning

confidence: 62%

Very Small Embryonic-Like Stem Cells Survive and Restore Spermatogenesis after Busulphan Treatment in Mouse Testis

An¹,

Bhartiya²,

Sriraman³

et al. 2014

J Stem Cell Res Ther

View full text Add to dashboard Cite

Study Objectives: Adult mammalian testes harbor a novel population of quiescent, pluripotent, very small embryonic-like stem cells (VSELs) along with spermatogonial stem cells (SSCs). Present study was undertaken to (i) characterize testicular VSELs (ii) investigate differential effect of chemotherapy on VSELs and SSCs and (iii) to restore the differentiation ability of surviving VSELs by providing healthy somatic microenvironment.Methods: Effect of busulphan (25 mg/Kg) was studied on mouse testes. Syngenic Sertoli cells (10 5 cells per testis) and bone marrow derived mesenchymal cells (10 4 cells per testis) were transplanted separately through intertubular route. Effect of niche reconstruction was studied two months later by histology and immuno-localization of germ cell markers MVH and PCNA. Caudal sperm were evaluated for their ability to fertilize oocytes in vitro.Results: VSELs were 2-6 µm in size, SCA-1 + /CD45 -/LIN -, had high nucleo-cytoplasmic ratio and comprised 0.03% of testicular cells whereas SSC specific marker GFRa localized on a distinct, larger cell population. Busulphan selectively destroyed SSCs and other germ cells however, nuclear OCT-4A, Nanog, Sox-2 and SCA-1 positive VSELs (0.06%) survived. Persisting VSELs were unable to differentiate possibly because chemotherapy also affected the 'niche' comprising Sertoli cells. Complete restoration of spermatogenesis was observed two months post transplantation of Sertoli and mesenchymal cells. Transplanted cells formed neo-tubules in the vicinity of surviving tubules and were possibly a source of growth factors essential for VSELs proliferation and differentiation. Both MVH and PCNA showed increased staining in the transplanted group. qRT-PCR studies revealed existence of a meiotic block in busulphan treated testis which was overcome after transplantation. Resulting sperm progressed to epididymis, showed normal motility and ability to fertilize in vitro. Conclusion:Results show that VSELs survive chemotherapy and can restore spermatogenesis in germ cells depleted mice. Results have direct relevance to address fertility issues of cancer survivors.

show abstract

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

Cited by 8 publications

References 57 publications

In Vivo Differentiation of Therapeutic Insulin-Producing Cells from Bone Marrow Cells via Extracellular Vesicle-Mimetic Nanovesicles

In Vivo Differentiation of Therapeutic Insulin-Producing Cells from Bone Marrow Cells via Extracellular Vesicle-Mimetic Nanovesicles

Murine Sca1+Lin− bone marrow contains an endodermal precursor population that differentiates into hepatocytes

Very Small Embryonic-Like Stem Cells Survive and Restore Spermatogenesis after Busulphan Treatment in Mouse Testis

Contact Info

Product

Resources

About