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 虽然诱导性多能干细胞(iPSC)和胚胎干细胞(ESC)在细胞来源上有所不同,但具有分化为任何细胞类型的能力,这使得它们成为细胞疗法和细胞生物学研究的理想之选。干细胞生长因子,如碱性成纤维细胞生长因子FGF-basic 通过对细胞生存、凋亡和增殖的遗传调控,维持多能干细胞的培养。骨形态发生蛋白-4(BMP-4)等重组蛋白也用于阻断多能干细胞培养中的不需要的分化。

用于多能干细胞培养和更新的重组蛋白:

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].

表 1.用于淋巴细胞分化的重组干细胞生长因子

蛋白质淋巴细胞来源的细胞类型
B 细胞NK 细胞
T细胞
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  

表 2.用于髓系细胞分化的重组干细胞生长因子

蛋白质髓源性细胞类型
中性粒细胞嗜酸性粒细胞嗜碱性粒细胞巨噬细胞树突状细胞
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 间充质干细胞(MSC)是在骨髓和其他血管化组织中发现的多能血管外膜细胞。在接触不同的间充质干细胞添加剂后,这些细胞通过细胞信号转导途径(如软骨生成、脂肪细胞生成、肌发生和骨发生)发生改变。

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].

表 3.用于间充质干细胞分化的重组生长因子

蛋白质软骨细胞骨细胞肌细胞脂肪细胞
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-β 1
VEGF-165   


Growth factors and cytokines for differentiating other progenitor cells

NSC cartoon 

用于神经细胞分化的干细胞生长因子和细胞因子

神经干细胞是多能干细胞,可产生神经系统的主要表型。基底细胞、神经胶质细胞和神经元干细胞祖细胞分化为中枢神经系统细胞,如运动神经元和周围神经元或星形胶质细胞。

表 4.用于神经干细胞更新和神经胶质祖细胞分化的重组生长因子

蛋白质神经干细胞更新胶质祖细胞
星形胶质细胞 III 型星形胶质细胞少突胶质细胞
CNTF 
EGF
FGF-basic (FGF-2/bFGF)
IGF-1   
NT-3   
PDGF AA/BB/AB 
Sonic Hedgehog C25II (SHH)  

表 5.用于基底细胞和神经元限制性祖细胞分化的神经元细胞的重组生长因子

蛋白质基底祖细胞神经元限制性祖细胞
运动神经元外周神经元多巴胺能神经元谷氨酸能神经元GABA能神经元
BDNF  
β-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) 

用于分化为其他祖细胞的生长因子和细胞因子

iPSC/ESC 可以通过三胚层在体内分化为任何细胞谱系。虽然在体外所有人体组织中复制这些过程存在挑战,但通过生长因子的正确组合,可以驱动 iPSC/ESC 分化为对疾病模型研究 (包括肺细胞、肠道细胞、胰腺细胞、甲状腺细胞和肝细胞) 至关重要的许多细胞类型。

表 6. 其他干细胞分化驱动的重组蛋白

 蛋白质肠道胰腺肝脏甲状腺
激活素A  
BMP-4   
EGF  
FGF-10  
FGF-4    
FGF-7 (KGF)    
FGF-basic (FGF-2/bFGF)    
HGF    
Noggin  
R-Spondin   
TGF-β 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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