Red blood cell transfusion is an effective method to treat acute hemorrhage and severe anemia. However, blood source from donors is very limited, and transfusion-transmitted diseases occurred frequently, thus threatening human health. Therefore, the safe, abundant and functional blood source is needed. Generation of blood cells from human pluripotent stem cells(hPSC) will offer alternative approach. Lots of studies have been focused on erythroid cell differentiation in vitro, including how to enhance efficiency and improve their function. In this review, the research advances on differentiation methods and the regulatory mechanism are summarized. In addition, the progress in PSC differentiation into erythrocytes and the problems to be solved are discussed briefly.
Cell Differentiation ; Embryonic Stem Cells ; cytology ; Erythrocytes ; cytology ; Humans ; Induced Pluripotent Stem Cells ; cytology

Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have the potential of differentiating into all types of adult cells. Today, mature functional sperm can be derived from mouse PSCs in vitro, and meanwhile primordial germ cells (PGCs) and meiotic prophase sperm cells can be generated from human ESCs/iPSCs (hESCs/hiPSCs). It is proposed that non-genetic azoospermia might be cured if functional sperm could be obtained from human PSCs (hPSCs) in vitro. It is also possible that healthy functional sperm could be derived from the patient with genetic factor-induced azoospermia by combining iPSCs and gene editing technology. IPSC-derived functional sperm have a higher clinical value for the avoidance of the sperm source and the issue of medical ethics. This article summarizes recent advances in the differentiation of PSCs into male germ cells in vitro, aiming to provide some reference for the treatment of male infertility with PSCs.
Animals ; Cell Differentiation ; Embryonic Stem Cells ; cytology ; Humans ; Induced Pluripotent Stem Cells ; cytology ; Infertility, Male ; therapy ; Male ; Meiosis ; Mice ; Pluripotent Stem Cells ; cytology ; Spermatozoa ; cytology

At present, it is generally believed that the paracrine effect of stem cells in the repair of myocardial injury is one of the important ways for stem cell therapy. Exosomes are phospholipid bilayer-enclosed nanovesicles that secreted by cells under physiological and pathological conditions. Cargo loaded into exosomes including protein, lipids and nucleic acids can be delivered to recipient cells. Therefore, exosomes are recognized as important mediators for intercellular communication. It has been suggested that exosomes from stem cells (eg. embryonic stem cells, induced pluripotent stem cells, cardiac progenitor cells, mesenchymal stem cells and cardiosphere-derived cells) have protective effects against heart injury. In this review, we summarized recent research progresses on stem cell-derived exosomes in myocardial injury, including the therapeutic effects and mechanism.
Cell Communication ; Exosomes ; physiology ; Heart Injuries ; Humans ; Induced Pluripotent Stem Cells ; cytology ; Mesenchymal Stem Cells ; cytology

Human pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement. These human PSCs, similar to their counterparts of mouse, have the full potential to give rise to any type of cells in the body. However, for the promise to be fulfilled, it is necessary to convert these PSCs into functional specialized cells. Using the developmental principles of neural lineage specification, human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia, such as striatal gama-aminobutyric acid (GABA)-ergic neurons, spinal motor neurons and myelin sheath forming oligodendrocytes. The human PSCs, in general differentiate after the similar developmental program as that of the mouse: they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition. However, the human PSCs, unlike their counterparts of mouse, tend to respond divergently to the same set of extracellular signals at certain stages of differentiation, which will be a critical consideration to translate the animal model based studies to clinical application.
Astrocytes ; cytology ; Cell Differentiation ; Embryonic Stem Cells ; cytology ; Humans ; Neuroglia ; cytology ; Neurons ; cytology ; Pluripotent Stem Cells ; cytology

Male germ stem cells (mGSCs), which is in testis after sex differentiation, derive from primordial germ cells. In this study, bovine mGSCs were isolated from testis of 20 weeks fetuses. Number of CD9 positive cells of the cells through two-steps adhering plates velocity different was 95.8% by flow cytometer. The carina-type cells clones and the plane-type cells clones appeared in co-cultured system. One cells lines had been successively maintained for 4 passages, and the cells clusters showed AKP positive staining. The cells clusters showed nest-shape in third passage showed SSEA1 and Oct-4 positive staining. These cells can also spontaneously differentiate into c-kit positive staining germ cells, and the cells were directional induced to formaactin positive staining cardiac-like cells cluster and NF positive staining neuron-like cells. The conclusion showed that male germ stem cells from 20 weeks bovine fetuses could be in vitro formed like embryonic stem cells.
Animals ; Cattle ; Cell Differentiation ; physiology ; Cells, Cultured ; Embryonic Stem Cells ; cytology ; Fetus ; cytology ; Male ; Pluripotent Stem Cells ; cytology ; Spermatozoa ; cytology

Recent studies have confirmed that diverse adult tissue cells can be reprogrammed and induced to pluripotency, that is so-called induced pluripotent stem cells (iPS cells). But most of these dedifferentiated processes are induced by gene delivery with retroviral vectors. Some of the delivered genes are cancer causing. So, in current situation, these adult-derived embryonic stem-like cells cannot be used in clinical therapy to cure human diseases. Recently some articles that were published in the authoritative journals are receiving attentions. They show that, in mice and human, spermatogonial stem cells (SSCs) can be used for generating pluripotent stem cells without the exogenous genes and retroviruses, and they can also be used for autologous transplantation without ethical problems. These findings suggest that human SSCs may have considerable potential for cell-based, autologous organ regeneration therapy for various diseases. In this review, we describe and compare the methods that have been used to isolate, purificate and culture SSCs. We also describe the recent results in which SSCs can be transformed into pluripotent stem cells, and the pluripotent stem cells have potential applications in regenerative medicine and genetic medicine.
Cell Culture Techniques ; methods ; Cell Dedifferentiation ; physiology ; Cells, Cultured ; Humans ; Male ; Pluripotent Stem Cells ; cytology ; Spermatogonia ; cytology ; Stem Cells ; cytology

Stem cell research is a innovative technology that focuses on using undifferentiated cells able to self-renew through the asymmetrical or symmetrical divisions. Three types of stem cells have been studied in laboratory including embryonic stem cell, adult stem cells and induced pluripotent stem cells. Embryonic stem cells are pluripotent stem cells derived from the inner cell mass and it can give rise to any fetal or adult cell type. Adult stem cells are multipotent, have the ability to differentiate into a limited number of specialized cell types, and have been obtained from the bone marrow, umbilical cord blood, placenta and adipose tissue. Stem cell therapy is the most promising therapy for several degenerative and devastating diseases including digestive tract disease such as liver failure, inflammatory bowel disease, Celiac sprue, and pancreatitis. Further understanding of biological properties of stem cells will lead to safe and successful stem cell therapies.
Adult Stem Cells/cytology/metabolism/transplantation ; Embryonic Stem Cells/cytology/metabolism/transplantation ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism/transplantation ; Stem Cells/*cytology/metabolism

OBJECTIVETo reprogram amniotic fluid cells into pluripotent stem cells in order to create an optimal internal control model for directed cell differentiation.

METHODSHuman amniotic fluid-derived cells (hAFDCs) from heterozygotic twin fetuses were induced by retroviral vectors encoding Oct4, Sox2, c-Myc and Klf4. In vivo pluripotency, differentiation capacity and karyotype of hAFDCs induced pluripotent stem cells (hAFDCs-iPSCs) were determined.

RESULTShAFDC-iPSCs derived from heterozygotic twins have maintained self renewal, with expression of high pluripotency marker gene detected at both mRNA and protein levels. The cells have maintained their differentiation capacity both in vitro and vivo, and showed normal karyotypes after long-term culturing in vitro.

CONCLUSIONhAFDCs-iPSCs derived from heterozygotic twins have good consistency in terms of genetic background, and can provide a good internal control for directed differentiation of iPSCs, and may be used an ideal source for autologous cell replacement therapy in the later life of the fetus.

Amniotic Fluid ; cytology ; metabolism ; Cell Differentiation ; genetics ; Cell Line ; Female ; Fetus ; metabolism ; Heterozygote ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Karyotype ; Pluripotent Stem Cells ; cytology ; metabolism ; Pregnancy ; Twins

The basic studies selected were mainly published since 1998 and related to stem cell biology and engineering and particularly the efforts for developing new sources of hematopoietic stem/progenitor cells ex vivo. Hematopoietic cells and lymphocytes can be developed by induced differentiation in a appropriate way of culture, originating in the embryo- or adult-derived stem cells or tissue-committed stem cells which still exist in the tissue of adults. The most primitive multipotential embryonic stem cell from embryo or adult tissue has the plasticity to differentiate into every kind of progenies, the committed tissue-specific stem cell, by different proper ways of induction in vitro. The committed tissue-specific stem cell, however, can only be induced to differentiate along the line of its committed origin of tissue. No studies in China strongly confirmed yet the existence of "transdifferentiation" among the tissue- or organ-specific stem cells.
Adult ; Cell Differentiation ; Cell Lineage ; China ; Embryo, Mammalian ; cytology ; Hematopoietic Stem Cells ; cytology ; Humans ; Mesoderm ; cytology ; Models, Biological ; Pluripotent Stem Cells ; cytology ; Research ; trends ; Stem Cells ; cytology

As the theory of stem cell plasticity was first proposed, we have explored an alternative hypothesis for this phenomenon: namely that adult bone marrow (BM) and umbilical cord blood (UCB) contain more developmentally primitive cells than hematopoietic stem cells (HSCs). In support of this notion, using multiparameter sorting we were able to isolate small Sca1+Lin-CD45- cells and CD133+Lin-CD45- cells from murine BM and human UCB, respectively, which were further enriched for the detection of various early developmental markers such as the SSEA antigen on the surface and the Oct4 and Nanog transcription factors in the nucleus. Similar populations of cells have been found in various organs by our team and others, including the heart, brain and gonads. Owing to their primitive cellular features, such as the high nuclear/cytoplasm ratio and the presence of euchromatin, they are called very small embryonic-like stem cells (VSELs). In the appropriate in vivo models, VSELs differentiate into long-term repopulating HSCs, mesenchymal stem cells (MSCs), lung epithelial cells, cardiomyocytes and gametes. In this review, we discuss the most recent data from our laboratory and other groups regarding the optimal isolation procedures and describe the updated molecular characteristics of VSELs.
Animals ; Cell Lineage ; Cell Separation/*methods ; Embryonic Stem Cells/*cytology/metabolism ; Hematopoietic Stem Cells/*cytology/metabolism ; Humans ; Mesenchymal Stromal Cells/*cytology/metabolism ; Pluripotent Stem Cells/cytology/metabolism