Stem Cell Therapy Growth Factors & Cytokines

Stem cell therapies have been expected to bring substantial benefit to patients suffering a wide range of diseases and injuries. Stem cells are not only known to express various growth factor (cytokine) receptors, but also respond to various cytokines by activation of conventional cytokine signaling pathways. Despite their pluripotent advantage, stem cells appear to be regulated by growth factors in the same manner as other immune cells. The characterization of many growth factors that control hematopoiesis, osteogenesis or neuropoiesis has led to intense investigation to find out potential use of these cytokines for ex vivo expansion of various types of stem cells.
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Growth Factors Regulating Different Stem Cells

Hematopoietic stem cells

Hematopoietic stem cell therapy growth factors (cytokines) are responsible for the regulation of the multiple fates of hematopoietic stem cells – including quiescence, self-renewal, differentiation, apoptosis, and mobilization from the niche – requires the cooperative actions of several growth factors and other hormones that bind to receptors on these cells.

Mesenchymal stem cells

Mesenchymal stem cells (MSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage. Growth factors regulate mesenchymal stem cell functions more than any other molecule and they play an important role in the proliferation, differentiation, or other properties of mesenchymal stem cells, either alone or in combination of other growth factors (cytokines).

Embryonic / pluripotent stem cells

Embryonic / pluripotent stem cells are ideal candidates for novel stem cell therapy because it can differentiate into any cell type. Many Growth Factors (Cytokines) have overlapping, pleiotropic effects on a variety of different cell types and activate target genes involved in survival, apoptosis, proliferation and differentiation, as well as suppression of differentiation.

Neural stem cells

Growth factors (cytokines) play an important role in determining the inflammatory microenvironment and have also been shown to have effects on the differentiation, proliferation, migration and survival of Neural stem cells. These growth factors have been shown to alter neural stem cell self-renewal and progenitor cell division and differentiation

Vital Stem Cell Therapy Growth Factors & Cytokines

IL-3

The human interleukin-3 (hIL-3) is a glycoprotein, which served as a key modulation factor of primitive hematopoietic cell proliferation and differentiation. It was also demonstrated that IL-3 enhances human osteoblast differentiation and bone formation in both in vitro and in vivo conditions

SCF

Stem cell factor (SCF, also called Steel factor or Kit ligand) is a growth factor that exists both as a membrane-bound and soluble form. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival, and differentiation of hematopoietic progenitors, melanocytes, and germ cells.

IL-6

IL-6 was originally identified as a T cell-derived factor, which induced the final maturation of B lymphocytes into antibody-forming plasma cells. IL-6 functions neural stem/progenitor cells by binding to the soluble form of IL-6R and then bind directly to the gp130 receptor.

GM-CSF

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in the generation of granulocytes, macrophages, and dendritic cells from hematopoietic stem cells. It was also identifeid as a neuronal growth factor in the brain and a factor involved in arteriogenesis after brain ischemia.

LIF

LIF is capable of maintaining embryonic stem (ES) cells in a pluripotent state through promoting self-renewal or suppressing stem cell differentiation. It has become a standard protocol to use LIF to maintain murine embryonic stem cell pluripotency, whereas withdrawal of LIF allows embryonic stem cells to undergo cell differentiation

G-CSF

The ability to mobilize hematopoietic stem cells from the bone marrow into the blood of G-CSF changes the face of hematopoietic stem cell transplantation. It was among the first growth factors to be identified and rapidly transitioned into clinical medicine.

EPO

Erythropoietin (EPO) is a glycoprotein that regulates the growth and differentiation of erythroid progenitor cells. In addition, Erythropoietin (EPO) was reportedly to mediates the proliferation and apoptosis of a variety of non-hematopoietic cells through the erythropoietin receptor (EPOR).

Flt3-ligand

Flt3-Ligand has an effect on early B cell development as well as on T cell development, at least in the embryo. It was shown that intracellular Flt3 receptors have been found to exist in human mesenchymal stem cells and expansion of human mesenchymal stem cells is highly dependant on the time, duration and concentration of Flt3-Ligand.

TPO

TPO augmented survival and proliferation of CD34+ haematopoietic stem or progenitor cells, especially when used in combination with IL3 or SCF. TPO also plays a role in haematopoietic stem cell maintenance in humans. TPO can augment ex vivo expansion of haematopoietic stem cells to increase the pool available for transplantation

M-CSF

M-CSF acts on hematopoiesis by promoting the growth of monocyte/macrophage colonies from human blood CD34+ progenitor cells and high proliferation colony-forming cells.. It was also shown that M-CSF can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change

FGF-2

FGF-2 is expressed mostly in tissues of mesoderm and neuroectoderm origin, and is thought to play an important role in the mesoderm induction. In recent years, a number of studies have identified fibroblast growth factors FGF-2 as key regulator of a variety of stem cell types.

TGF beta

In most cell types, TGF-beta signaling additionally controls the expression of a plethora of homeostatic genes whose activity determines cell proliferation, extracellular matrix production, paracrine factor secretion, cell–cell contacts, immune function, and tissue repair.

Hematopoietic stem cells

Hematopoietic stem cell therapy growth factors (cytokines) are responsible for the regulation of the multiple fates of hematopoietic stem cells – including quiescence, self-renewal, differentiation, apoptosis, and mobilization from the niche – requires the cooperative actions of several growth factors and other hormones that bind to receptors on these cells.

Mesenchymal stem cells

Mesenchymal stem cells (MSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage. Growth factors regulate mesenchymal stem cell functions more than any other molecule and they play an important role in the proliferation, differentiation, or other properties of mesenchymal stem cells, either alone or in combination of other growth factors (cytokines).

Embryonic / pluripotent stem cells

Embryonic / pluripotent stem cells are ideal candidates for novel stem cell therapy because it can differentiate into any cell type. Many Growth Factors (Cytokines) have overlapping, pleiotropic effects on a variety of different cell types and activate target genes involved in survival, apoptosis, proliferation and differentiation, as well as suppression of differentiation.

Neural stem cells

Growth factors (cytokines) play an important role in determining the inflammatory microenvironment and have also been shown to have effects on the differentiation, proliferation, migration and survival of Neural stem cells. These growth factors have been shown to alter neural stem cell self-renewal and progenitor cell division and differentiation

Stem Cell Therapy Cytokines & Growth Factors Reference

• Singh G, et al. Cytokine regulation of stem cells[R]. PeerJ Preprints, 2016.
• Trounson A, et al. Stem cell therapies in clinical trials: progress and challenges[J]. Cell Stem Cell, 2015, 17(1): 11-22.