Stem cell growth factors and cytokines play key roles in healthy stem cell cultures. Some maintain pluripotency, enable self-renewal, and prevent spontaneous differentiation of ESCs and iPSCs, whereas other growth factors reprogram stem cells through protein-mediated initiation or inhibition of cell signaling pathways.


Gibco PeproTech recombinant proteins for stem cell culture and differentiation

Thermo Fisher Scientific offers stem cell growth factors, cytokines, and other stem cell-related recombinant proteins in the PeproTech portfolio to effectively maintain, expand, and differentiate stem cells into desired phenotypes.


Explore stem cell-related cytokines and growth factors by cell type


Stem cell growth factors and cytokines for maintaining pluripotency

PSCs cartoon Induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) cultures differ in cell source but share the ability to differentiate into any cell type, making them ideal candidates for cell therapy and cell biology studies. Stem cell growth factors such as FGF-basic maintain pluripotent stem cell cultures through genetic regulation of cellular survival, apoptosis, and proliferation. Recombinant proteins such as BMP-4 are also used to block unwanted differentiation in pluripotent stem cell cultures.

Pluripotent stem cell culture and renewal proteins

Functional groupFactor / CytokinePrimary role in pluripotency
Self-renewal & pluripotency maintenanceFGF-basic (FGF-2/bFGF)Promotes proliferation and supports self-renewal of human pluripotent stem cells by suppressing spontaneous differentiation [1].
NanogCore transcription factor maintaining pluripotency; prevents differentiation into somatic lineages [2].
Sox2Regulates expression of pluripotency genes with Oct4 and Nanog; essential for maintaining undifferentiated state [3].
TGF-betaSustains pluripotency through SMAD2/3 signaling; cooperates with FGF to prevent differentiation[4].
Differentiation & lineage specificationBMP-4Induces mesoderm and trophectoderm differentiation; balances pluripotency and lineage specification with FGF/TGF-β signals [5].
Wnt-3aModulates pluripotency and germ layer specification via canonical Wnt/β-catenin signaling [6].
Extracellular matrix supportVitronectinProvides a defined, xeno-free substrate for PSC attachment and growth; supports long-term undifferentiated culture [7].


Stem cell cytokines and growth factors for hematopoietic cell differentiation

HSC cartoon Hematopoietic stem cells (HSC) differentiate into all blood cell types from the myeloid and lymphoid lineages. The cytokine IL-7 drives HSCs to differentiate into lymphoid progenitors, whereas combination of the cytokine IL-3 and stem cell growth factor GM-CSF sends HSCs down the myeloid lineage. Supplementing lymphoid stem cell cultures with other cytokines and growth factors drives differentation into immune cell types like T cells, B cells, and NK cells. By application of the correct combination of growth factors, myeloid stem cell cultures can be differentiated into neutrophils, macrophages or dendritic cells.


Stem cell growth factors for HSC renewal

Functional groupCytokine / Growth factorPrimary role in hematopoiesis
Lineage-specific differentiation & survivalIL-2Drives proliferation and activation of mature T lymphocytes; regulates immune tolerance and effector function [8].
IL-4Promotes B cell activation and antibody class switching; supports Th2-type T-cell differentiation [9].
IL-7Essential for lymphoid progenitor survival and differentiation, especially B and T cell development [10].
Stem cell maintenance & proliferationSCF (Stem cell factor)Promotes survival, self-renewal, and proliferation of hematopoietic stem and progenitor cells via c-Kit receptor signaling [11].
TPO (Thrombopoietin)Regulates HSC quiescence, expansion, and megakaryocyte differentiation; maintains stem cell pool in bone marrow [12].
Early hematopoietic progenitor expansionIL-3Stimulates proliferation and differentiation of multipotent progenitors into myeloid and erythroid lineages; synergizes with SCF and IL-6 [11].
IL-6Supports HSC proliferation and myeloid lineage commitment; modulates inflammatory regulation of hematopoiesis [13].

Table 1. Recombinant stem cell growth factors for lymphoid cell differentiation

ProteinLymphoid-derived cell type
B cellNK cell
T cell
G-CSF 
IL-1 
IL-10  
IL-11  
IL-12  
IL-2
IL-3  
IL-4 
IL-5  
IL-6 
IL-7
IL-9  
LIF  
M-CSF  

Table 2. Recombinant stem cell growth factors for myeloid cell differentiation

ProteinMyeloid-derived cell type
NeutrophilEosinophilBasophilMacrophageDendritic cell
FLT-3 ligand (FLT3L)    
G-CSF 
GM-CSF
IFN-gamma    
IL-3
IL-4
IL-5    
M-CSF   


Stem cell cytokines and growth factors for mesenchymal cell differentiation

MSCs cartoon Mesenchymal stem cells (MSCs) cells are multipotent, perivascular cells found in bone marrow and other vascularized tissues. Given exposure to different mesenchymal stem cell supplements these cells undergo changes via cell signaling pathways such as chondrogenesis, adipogenesis, myogenesis, and osteogenesis.

Stem cell growth factors for MSC proliferation and renewal

Functional groupCytokine / Growth factorPrimary role in MSCs
MSC proliferation & maintenanceEGF (Epidermal growth factor)Stimulates MSC proliferation and supports osteogenic and chondrogenic differentiation through ERK signaling [14].
FGF-basic (FGF-2/bFGF)Enhances MSC proliferation, maintains multipotency, and delays senescence during in vitro expansion [15].
LIF (Leukemia inhibitory Factor)Modulates MSC self-renewal and suppresses differentiation through STAT3 signaling; supports pluripotent state in embryonic stem cells [16].
Differentiation & lineage commitmentHGF (Hepatocyte growth factor)Enhances MSC motility, survival, and differentiation toward epithelial and endothelial phenotypes; promotes tissue repair [17].
PDGF-BB (Platelet-derived growth factor-BB)Promotes MSC migration, proliferation, and differentiation into smooth muscle and perivascular cells [18].
Wnt-3aDirects osteogenic lineage commitment via canonical Wnt/β-catenin signaling; inhibits adipogenic differentiation [19].

Table 3. Recombinant growth factors for mesenchymal stem cell differentiation

ProteinChondrocyteOsteocyteMyocyteAdipocyte
BMP-2  
BMP-4  
BMP-6   
BMP-7   
CCL8 (MCP-2)   
CXCL9   
FGF-10   
FGF-4   
FGF-8   
FGF-9   
FGF-basic (FGF-2/bFGF)
FLT-3 ligand (FLT3L)  
IGF-1   
IL-1   
IL-11   
IL-15   
IL-6   
IL-7  
IL-8 (CXCL8)  
LIGHT   
M-CSF   
TRANCE (RANKL)   
CXCL12 (SDF-1a)   
TGF-beta 1
VEGF-165   


Growth factors and cytokines for differentiating other progenitor cells

NSC cartoon 

Stem cell growth factors and cytokines for neural cell differentiation

Neural stem cells are multipotent stem cells that produce the main phenotypes of the nervous system. Basal, glial, and neuronal stem cell progenitors differentiate into the cells of the central nervous system like motor and peripheral neurons or astrocytes.

Table 4. Recombinant growth factors for neural stem cell renewal and glial progenitor differentiation

ProteinNeural stem cell renewalGlial progenitor
Astrocyte IType II astrocyteOligodendrocyte
CNTF 
EGF
FGF-basic (FGF-2/bFGF)
IGF-1   
NT-3   
PDGF AA/BB/AB 
Sonic Hedgehog C25II (Shh)  

Table 5. Recombinant growth factors for neuronal cell differentiation from basal and neuron-restricted progenitors

ProteinBasal progenitorNeuron-restricted progenitor
MotorPeripheralDopaminergicGlutamatergicGABAergic
BDNF  
beta-NGF    
BMP-2    
BMP-4    
EGF   
FGF-10   
FGF-4    
FGF-8b   
FGF-basic (FGF-2/bFGF)
GDNF   
IGF-1   
NT-4    
PDGF AA/BB/AB  
Sonic Hedgehog C25II (Shh) 

Growth factors and cytokines for differentiating other progenitor cells

iPSC/ESC can differentiate into any cell lineage via the three germ layers in vivo. While challenges exist to replicate these processes in vitro across all human tissues, with the right combination of growth factors iPSC/ESC can be driven to differentiate into numerous cell types important for disease model research including lung, gut, pancreatic, thyroid, and hepatic cells.

Table 6. Other stem cell differentiation-driving recombinant proteins

 ProteinLungGutPancreaticHepaticThyroid
Activin A  
BMP-4   
EGF  
FGF-10  
FGF-4    
FGF-7 (KGF)    
FGF-basic (FGF-2/bFGF)    
HGF    
Noggin  
R-Spondin   
TGF-beta 1    
Wnt-3a    
References
  1. Xu RH, Peck RM, Li DS, et al. (2005) Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods 2(3):185–190. 
  2. Chambers I, Silva J, Colby D, et al. (2007) Nanog safeguards pluripotency and mediates germline development. Nature 450(7173):1230–1234.
  3. Avilion AA, Nicolis SK, Pevny LH, et al. (2003) Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17(1):126–140. 
  4. James D, Levine AJ, Besser D, et al. (2005) TGFβ/Activin/Nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132(7):1273–1282. 
  5. Ying QL, Nichols J, Chambers I, et al. (2003) BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115(3):281–292. 
  6. Sato N, Meijer L, Skaltsounis L, et al. (2004) Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10(1):55–63. 
  7. Braam SR, Zeinstra L, Litjens S, et al. (2008) Recombinant vitronectin is a functionally defined substrate that supports human embryonic stem cell self-renewal via alphavbeta5 integrin. Stem Cells 26(9):2257–2265. 
  8. Malek TR, Castro I (2010) Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity 33(2):153–165. 
  9. Paul WE (1991) Interleukin-4: a prototypic immunoregulatory lymphokine. Blood 77(9):1859–1870. 
  10. Akashi K, Kondo M, Freeden-Jeffry U, et al. (1997) Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell 89(7):1033–1041. 
  11. Metcalf D (1995) The hematopoietic colony-stimulating factors. Cambridge University Press. 
  12. Kaushansky K (1995) Thrombopoietin: the primary regulator of platelet production. Blood 86(2):419–431. 
  13. Mirantes C, Passegué E, Pietras EM (2014) Pro-inflammatory cytokines: emerging players regulating HSC function in normal and diseased hematopoiesis. Exp Cell Res 329(2):248–254. 
  14. Tamama K, Fan VH, Griffith LG, et al. (2007) Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells. Stem Cells 24(3):686–695. 
  15. Tsutsumi S, Shimazu A, Miyazaki K, et al. (2001) Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 288(2):413–419. 
  16. Niwa H, Budon T, Chanbers I, et al. (1998) Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev 12(13):2048–2060. 
  17. Zarnegar R, Michalopoulos GK (1995) The many faces of hepatocyte growth factor: from hepatopoiesis to morphogenesis. J Cell Biol 129(5):1177–1180. 
  18. Mellgren AM, Smith CL, Olsen GS, et al. (2007) Platelet-derived growth factor receptor beta signaling is required for efficient epicardial cell migration and development of two distinct coronary vascular smooth muscle cell populations. Circ Res 103(12):1393–1401. 
  19. Boland GM, Perkins G, Hall DJ, et al. (2004) Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Biol Chem 93(6):1210–1230. 

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