Cited by 129Mesenchymal stem cell researchNeurogenesis and neuroplasticity mechanismsPluripotent Stem Cells Research

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IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells

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Huat, Tee Jong, Khan, Amir Ali, Pati, Soumya, Mustafa, Zulkifli, Abdullah, Jafri Malin, Jaafar, Hasnan·2014·BMC Neuroscience

DOI 10.1186/1471-2202-15-91PMC PMC4117972

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Abstract

BACKGROUND: There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells. RESULTS: The four derived NPCs showed a significantly higher expression of nestin than was shown by the negative control. Among the groups treated with growth factors, NPCs treated with IGF-1 showed the highest expression of nestin. Furthermore, NPCs derived using IGF-1 exhibited the highest cell proliferation and cell survival among the treated groups. The NPCs derived from IGF-1 treatment also resulted in a better yield after the terminal differentiation into neurons and glial cells than that of the other treated groups. CONCLUSIONS: Our results suggested that IGF-1 has a crucial role in the differentiation of MSCs into neuronal lineage by enhancing the proliferation and reducing the apoptosis in the NPCs. This information will be beneficial in the long run for improving both cell-based and cell-free therapy for neurodegenerative diseases.

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Figure 1 Phenotypic analysis of bone marrow mesenchymal stem cells. (A) Primary rat bone marrow MSCs attached to the surface of the flask exhibiting elongation (arrow). (B) Homogenous rat BM MSCs at passage 4 displaying a fibroblast-like appearance and spindle-like arrangement. (C-D) Immunofluorescence of BM MSCs showing a strong expression of CD90 (C) and CD44 (D). (E) BM MSCs showing weak expression of nestin. (F) Immunophenotypes of BM MSCs analysed by flow cytometry. Images were viewed at 400× magnification using an inverted microscope and a fluorescence microscope equipped with a pseudo-fluorescence filter.CC BY · PubMed Central

Figure 2 Neurospheres at days 1, 3, and 5 showing differing sizes in different combination of growth factors. Group A (EGF + bFGF); Group B (EGF + bFGF + IGF-1); Group C (EGF + bFGF + LIF); Group D (EGF + bFGF + BDNF) and Group E (no growth factors). Cells in Group E attached to the flask starting to differentiate (arrows). Neurospheres with irregular shape formed in Group E on day 5 of culture. Images were viewed with 100× magnification under an inverted microscope.CC BY · PubMed Central

Figure 3 Immunocytochemical staining and flow cytometer analysis of MSC-induced neural progenitor-like cells. (A) NPCs from group B (EGF + bFGF + IGF-1) strongly expressing nestin. (B) NPCs from group B also strongly express Sox-2. (C) Flow cytometer analysis of nestin expression of NPCs from all groups (A, B, C and D) indicating the early differentiation of MSCs into NPCs. Group E clearly show the existence of two populations of cells indicating partial differentiation due to the effect of neural basal media. Flow cytometric data further validated the results obtained from immunofluorescence staining for group B. Images were viewed at 100× magnification using a fluorescence microscope.CC BY · PubMed Central

Figure 4 Proliferation analyses of NPCs under different growth factors. Cells (n = 12) were incubated with MTS reagent for 4 hr and changes in proliferation were studied at five time intervals (24 hr, 48 hr, 72 hr, 96 hr, and 120 hr). The data represented as optical density (OD) at 540 nm in mean ± SEM (p < 0.05).CC BY · PubMed Central

Figure 5 Pairwise multiple comparison analyses between groups of NPCs at different time intervals. Pairwise multiple comparison analysis was carried out using Tukey’s HSD (Tukey’s honest significant difference test). The data in red represents mean ± SD for statistically significant results (p < 0.05). P-values stated in blue indicate statistically insignificant comparisons (p > 0.05).CC BY · PubMed Central

Figure 6 Apoptosis assay. Immunostaining revealed that transdifferentiation is associated with apoptotic activities. (A) SYTOX Blue nuclei staining, (B) FITC-conjugated Annexin V, (C) propidium iodide (PI), and (D) overlay image. All images are viewed at 40× magnification under a confocal microscope.CC BY · PubMed Central

Figure 7 Comparison of apoptotic activities between groups ( n = 3). (A) Percentage of live cells. (B) Percentage of necrotic cells. (C) Percentage of early apoptotic cells. (D) Percentage of late apoptotic cells. The data are presented as mean ± SD for statistically significant results (p < 0.05) and were obtained by flow cytometry equipped with analytical software.CC BY · PubMed Central

Figure 8 Quantitative RT-PCR analysis ( n = 3). (A) Expression plots of the nestin gene (green), the neurofilament gene (red) and the housekeeping gene (orange). (B) Histograms showing quantification of NES and NEFL at the indicated time. Results are expressed as the mean ± SD. *p < 0.05.CC BY · PubMed Central

Figure 9 In vitro differentiation of NPCs into neuronal cell types. NPCs from group A, B, C and D were differentiated at day 3 post induction using glial induction and neuronal induction protocol on poly-L-lysine coated wells for 14 days. All the NPCs from the four groups differentiated, attached to the surfaces and changed their morphology. The cells from negative control, Group E, were also treated similarly but the cells at the end of differentiation did not attach indicating no mature neural cells were formed.CC BY · PubMed Central

Figure 10 Immunocytochemical staining of terminally differentiated cells. NPCs from group B were differentiated using the neuronal induction medium and were stained with FluoroPan neuronal marker for neurons and astrocytes (GFAP). Nuclei have been counterstained with SYTOX Blue. (A) Phase contrast image of differentiated cells. (B) FluoroPan neuronal FITC. (C) Nucleus staining with SYTOX Blue. (D) Overlay image. (E) Astrocytes stained with GFAP and counterstained with secondary antibody Cy3. Images were taken at 400× magnification using a Pascal 5 confocal microscope (Carl Zeiss, Germany).CC BY · PubMed Central

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Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Méndez‐Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., MacArthur, B. D., Lira, S. A., Scadden, D. T., Ma’ayan, A., Enikolopov, G., & Frenette, P. S. (2010) · Nature · doi:10.1038/nature09262 · Cited by 3,381 · cited 1×
“ESCs are pluripotent cells derived from the inner cell mass of the blastocyst [4], whereas ASCs are isolated from adult tissues and defined as multipotent, since they are determined to produce cell types within their niche [5].”
Background
Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood
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“MSCs have also been found in most postnatal organs such as the umbilical cord, adipose tissue, peripheral blood, and amniotic fluid [9-11].”
Background
A Long-Term Follow-Up Study of Intravenous Autologous Mesenchymal Stem Cell Transplantation in Patients With Ischemic Stroke
Lee, J. S., Hong, J. M., Moon, G. J., Lee, P. H., Ahn, Y. H., & Bang, O. Y. (2010) · Stem Cells · doi:10.1002/stem.430 · Cited by 775 · cited 1×
“Autologous transplantation of MSCs in stroke patients was proven therapeutically effective [13].”
Background
Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation
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“has been reported that MSCs can be induced into neural lineage through several methods such as incubation with cytokines [19], co-culture with nerve cells [1,6], and transfection with known factors [20].”
Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells
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“This is consistent with the previous finding that one third of MSCs died after induction [14].”
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Plasticity of Cultured Mesenchymal Stem Cells: Switch from Nestin‐Positive to Excitable Neuron‐Like Phenotype
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Mesenchymal Stem Cells from Human Umbilical Cord Express Preferentially Secreted Factors Related to Neuroprotection, Neurogenesis, and Angiogenesis
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“Autologous transplantation of MSCs extracted from Wharton’s jelly has been reported to be free from immunogenic rejection [18].”
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Human bone marrow-derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro
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“However, recent studies suggested that ASCs, especially mesenchymal stem cells (MSCs) derived from bone marrow (BM), have intrinsic neurogenic potential and may be differentiated into mature cells of ectodermal origin [6-8].”
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Mesenchymal stem cells: A promising candidate in regenerative medicine
Chen, Y., Shao, J., Xiang, L., Dong, X.-J., & Zhang, G. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.01.007 · Cited by 254 · cited 1×
“The trans-lineage differentiation capability and unique immunogenic properties of MSCs have made them a potential alternative for cellular transplantation use in regenerative medicine [12].”
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Transplantation of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly after Complete Transection of the Rat Spinal Cord
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“MSCs may even release certain neurotrophic factors such as BDNF, nerve growth factor, and glial-derived neurotrophic factors [26,27], and it is well known that the neurotrophic factors are important for maintaining cellular survival of neuronal cells both in vitro and in vivo.”
Background

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Result
RETRACTED: Adult hippocampal neurogenesis (AHN) controls central nervous system and promotes peripheral nervous system regeneration via physical exercise
Zalouli, V., Rajavand, H., Bayat, M., Khaleghnia, J., Sharifianjazi, F., Jafarinazhad, F., & Beheshtizadeh, N. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115078 · Cited by 27
Retracted
Potential skin involvement in ALS: revisiting Charcot’s observation – a review of skin abnormalities in ALS
Paré, B., & Gros‐Louis, F. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0004 · Cited by 24
“It also reduces apoptosis and promotes cell proliferation as well as survival of differentiated neural progenitor-like cells derived from mesenchymal stem cells (Huat et al., 2014).”
Background
IGF-1 Gene Transfer to Human Synovial MSCs Promotes Their Chondrogenic Differentiation Potential without Induction of the Hypertrophic Phenotype
Ikeda, Y., Sakaue, M., Chijimatsu, R., Hart, D. A., Otsubo, H., Shimomura, K., Madry, H., Suzuki, T., Yoshikawa, H., Yamashita, T., et al. (2017) · Stem Cells International · doi:10.1155/2017/5804147 · Cited by 23
“IGF-1 promotes the proliferation of MSCs [24] and also leads to increased production of aggrecan and type 2 collagen and thus contributes to maintaining the phenotype of chondrocytes [23, 25].”
The factors affecting neurogenesis after stroke and the role of acupuncture
Mu, J.-D., Ma, L., Zhang, Z., Xu, Q., Zhang, Q., Ma, L.-H., & Sun, T. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1082625 · Cited by 22
“Insulin-like growth factor-1 (IGF-1) is a growth factor primarily produced by the liver in adults and plays a crucial role in cell proliferation, maturation, and survival (71).”
Background
Over-Expression of TRPC6 via CRISPR Based Synergistic Activation Mediator in BMSCs Ameliorates Brain Injury in a Rat Model of Cerebral Ischemia/Reperfusion
Li, W., Yang, F., Gao, J.-X., Tang, Y., Wang, J., & Pan, Y. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.06.041 · Cited by 20
The Roles of IGF-1 and MGF on Nerve Regeneration under Hypoxia- Ischemia, Inflammation, Oxidative Stress, and Physical Trauma
Sha, Y., Wang, C., Chen, L., Xu, C., Zhang, B., & Hong, H. (2022) · Current Protein and Peptide Science · doi:10.2174/1389203724666221208145549 · Cited by 19
Role of mTOR complex in IGF-1 induced neural differentiation of DPSCs
Huang, D. Y., Shen, S., Cai, M., Lin, J., Lü, J., Xu, K., Zhang, J., Feng, G., Hu, Y., Zheng, K., et al. (2019) · Journal of Molecular Histology · doi:10.1007/s10735-019-09825-z · Cited by 19
Improved Proliferative Capacity of NP-Like Cells Derived from Human Mesenchymal Stromal Cells and Neuronal Transdifferentiation by Small Molecules
Aguilera-Castrejon, A., Pasantes‐Morales, H., Montesinos, J. J., Cortés-Medina, L. V., Castro-Manrreza, M. E., Mayani, H., & Ramos‐Mandujano, G. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2086-7 · Cited by 18
“The floating structures formed by NP-like cells increase in size with time in culture, and this has been interpreted as evidence of cell proliferation [22].”
Background
Anti-apoptotic and pro-survival effect of exercise training on early aged hypertensive rat cerebral cortex
Liu, Y.-J., Cui, Z.-Y., Yang, A., Jallow, A. W., Huang, H., Shan, C., & Lee, S. (2021) · Aging · doi:10.18632/aging.203431 · Cited by 17
“Insulin-like growth factor (IGF-1) plays an essential role in promoting cell proliferation, differentiation and inhibiting neural apoptosis through the activation of PI3K/AKT signaling pathway [30].”
Background
Growth Factors and Their Application in the Therapy of Hereditary Neurodegenerative Diseases
Issa, S. S., Fayoud, H. J., Shaimardanova, A. A., Sufianov, A. A., Суфианова, Г. З., Solovyeva, V. V., & Rizvanov, A. A. (2024) · Biomedicines · doi:10.3390/biomedicines12081906 · Cited by 17
“…to regulate a wide variety of cellular processes on both intercellular and intracellular levels [2], including cell proliferation and survival [10], cell growth and differentiation [11], cell motility [12], metabolism regulation [13], and other functions that will be discussed later in this…”
Background
Proliferation and osteogenic differentiation of amniotic fluid-derived stem cells
Muduli, S., Lee, H. H., Yang, J.-S., Chen, T.-Y., Higuchi, A., Kumar, S. S., Alarfaj, A. A., Munusamy, M. A., Benelli, G., Murugan, K., et al. (2017) · Journal of Materials Chemistry B · doi:10.1039/c7tb01152k · Cited by 16
Odontogenesis and neuronal differentiation characteristics of periodontal ligament stem cells from beagle dog
Li, X., Liao, D., Sun, G., & Chu, H. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15158 · Cited by 16
Nonviral Reprogramming of Human Wharton's Jelly Cells Reveals Differences Between ATOH1 Homologues
Mellott, A. J., Devarajan, K., Shinogle, H. E., Moore, D. S., Talata, Z., Laurence, J. S., Forrest, M. L., Noji, S., Tanaka, E. I., Staecker, H., et al. (2015) · Tissue Engineering Part A · doi:10.1089/ten.tea.2014.0340 · Cited by 15
Human Fetal Bone Marrow-Derived Mesenchymal Stem Cells Promote the Proliferation and Differentiation of Pancreatic Progenitor Cells and the Engraftment Function of Islet-Like Cell Clusters
Li, X. Y., Wu, S. Y., & Leung, P. S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174083 · Cited by 15
Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia
Tan, S. H. D., Zhi, P. K., Luo, Z., & Shi, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.06.041 · Cited by 15
“As we all know, upregulation of insulin/insulin-like growth factors (IGF) signaling reinforced neurogenesis (Erickson et al., 2008; Speder et al., 2011; Supeno et al., 2013; Huat et al., 2014).”
CD29/CD184 expression analysis provides a signature for identification of neuronal like cells differentiated from PBMSCs
Fazeli, Z., Omrani, M. D., & Ghaderian, S. M. H. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.07.056 · Cited by 14
Current and Future Trends in Adipose Stem Cell Differentiation into Neuroglia
George, S., Hamblin, M. R., & Abrahamse, H. (2018) · Photomedicine and Laser Surgery · doi:10.1089/pho.2017.4411 · Cited by 14
Increasing proliferation of murine adipose tissue-derived mesenchymal stem cells by TNF-α plus IFN-γ
Mohammadpour, H., Pourfathollah, A. A., Zarif, M. N., & Hashemi, S. M. (2015) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923973.2015.1115519 · Cited by 14
The Effect of Endurance Training on Serum BDNF Levels in the Chronic Post-Stroke Phase: Current Evidence and Qualitative Systematic Review
Górna, S., & Domaszewska, K. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11123556 · Cited by 14
Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity
Park, S., Park, H.-L., Lee, S.-Y., & Jh, N. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.194 · Cited by 13
Weighted gene correlation network analysis reveals novel biomarkers associated with mesenchymal stromal cell differentiation in early phase
Xiao, B., Wang, G., & Li, W. (2020) · PeerJ · doi:10.7717/peerj.8907 · Cited by 13
“Gene miRNA BHLHE40 hsa-miR-374a-5p hsa-miR-8485 hsa-miR-4469 hsa-miR-454-3p FOXQ1 hsa-miR-378j hsa-miR-6507-3p hsa-miR-6839-5p hsa-miR-422a hsa-miR-6780a-3p hsa-miR-520h hsa-miR-1271-5p hsa-miR-520g-3p hsa-miR-506-3p HBEGF hsa-miR-4659a-3p hsa-miR-6868-3p hsa-miR-4659b-3p hsa-miR-30a-3p hsa-miR-30e-3p hsa-miR-4254 hsa…”
Influential
Hypoxia, a dynamic tool to amplify the gingival mesenchymal stem cells potential for neurotrophic factor secretion
Patil, S., Fageeh, H. N., Fageeh, H. I., Ibraheem, W., Alshehri, A. S., Albrakati, A., Almoammar, S., Almagbol, M., Dewan, H., Khan, S. S., et al. (2022) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2022.02.039 · Cited by 13
“The hypoxic environment also promoted osteogenic differentiation via the upregulation of growth factors (Hung et al., 2012) Hypoxia preconditioning is a widely adopted strategy as the concentration of O2 employed in in vitro conditions is high whereas the oxygen concentration in an ischemic…”
Background
Insulin‐like growth factor binding protein 4 inhibits proliferation of bone marrow mesenchymal stem cells and enhances growth of neurospheres derived from the stem cells
Li, H., Yu, S., Hao, F., Sun, X., Zhao, J., Xu, Q., & Duan, D. (2018) · Cell Biochemistry and Function · doi:10.1002/cbf.3353 · Cited by 13
“differentiation was initiated according to the protocols described by Huat et al.(3) The P4 BMSCs were harvested, seeded into a 24‐well plate (10(5) cells/cm(2)), and cultured in DMEM medium for 4 hours; the medium was subsequently replaced by NeuroCultTM NS‐A Basal Medium (Rat) and NeuroCultTM NS‐A Proliferation Supp…”
BackgroundMethodInfluential
Upregulated IGF‑1 in the lungs of asthmatic mice originates from alveolar macrophages
He, J., Mu, M., Wang, H., Ma, H., Tang, X., Fang, Q., Guo, S., & Song, C. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9726 · Cited by 13
Dysregulated Cardiac IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity
Aghdam, S. Y., Kenchegowda, D., Sharma, N. K., Holmes‐Hampton, G. P., Legesse, B., Moroni, M., & Ghosh, S. P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145049 · Cited by 12
Molecular Imaging for Comparison of Different Growth Factors on Bone Marrow-Derived Mesenchymal Stromal Cells’ Survival and ProliferationIn Vivo
Qiao, H., Zhang, R., Gao, L., Guo, Y., Wang, J., Zhang, R., Li, X., Li, C., Chen, Y., & Cao, F. (2016) · BioMed Research International · doi:10.1155/2016/1363902 · Cited by 11
Therapeutic effects of Wharton’s jelly-derived Mesenchymal Stromal Cells on behaviors, EEG changes and IGF-1 in rat model of the Parkinson’s disease
Jalali, M. S., Saki, G., Farbood, Y., Azandeh, S., Mansouri, E., Dehcheshmeh, M. G., & Sarkaki, A. (2021) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2021.101921 · Cited by 11
Exogenous insulin-like growth factor 1 attenuates sevoflurane anesthesia-induced cognitive dysfunction in aged rats
Xie, L. H., Fang, Q., Wei, X., Zhou, L., & Wang, S. (2021) · Journal of Neurophysiology · doi:10.1152/jn.00124.2021 · Cited by 11
Oral administration of cyclic glycyl-proline facilitates task learning in a rat stroke model
Kaneko, H., Namihira, M., Yamamoto, S., Numata, N., & Hyodo, K. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113561 · Cited by 11
Cell-Based Therapies for Glaucoma
Luis, J., Eastlake, K., Lamb, W. D. B., Limb, G. A., Jayaram, H., & Khaw, P. T. (2023) · Translational Vision Science & Technology · doi:10.1167/tvst.12.7.23 · Cited by 11
An Overview on Human Umbilical Cord Blood Stem Cell-Based Alternative In Vitro Models for Developmental Neurotoxicity Assessment
Singh, A. K., & Kashyap, M. P. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9202-6 · Cited by 11
Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression
Liermann-Wooldrik, K. T., Kosmacek, E. A., & Oberley‐Deegan, R. E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212137 · Cited by 11
“Additionally, adipocytes secrete insulin-like growth factor-1 (IGF-1) that stimulates angiogenic growth factors in endothelial cells and ASCs to proliferate and survive [26,27].”
Chondroitin sulfate/hyaluronic acid/carboxymethylcellulose macroporous cryogels for controlled delivery of TGF-β1 and IGF-1 to induce chondrogenic differentiation of adipose-derived stem cells in cartilage tissue engineering
Chen, C., Chang, C.-J., Kuo, C., Luo, G.-J., Dash, B. S., Govindaraju, D. T., & Chen, J. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.144756 · Cited by 9
Identification of IGF-1 Effects on White Adipose Tissue and Hippocampus in Alzheimer’s Disease Mice via Transcriptomic and Cellular Analysis
Kim, Y., Jo, D., Arjunan, A., Ryu, Y., Lim, Y.-H., Choi, S. Y., Kim, H. K., & Song, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052567 · Cited by 10
“Previous studies have shown that IGF-1 boosts neuronal cell differentiation and neuronal stem cell proliferation [100,101].”
Background
Distinctively Expressed Cytokines by Three Different Inflammation Cells and Their Interaction with Keratinocytes in Wound Healing
Wang, J., Wang, X., Chen, H., Liu, J., Tredget, E. E., & Wu, Y. (2017) · Inflammation · doi:10.1007/s10753-017-0655-9 · Cited by 9
“According to literature, IGF-1 plays significant roles in the differentiation of mesenchymal stem cells by enhancing the proliferation and reducing the apoptosis [41, 42].”
Background
From cord to caudate: characterizing umbilical cord blood stem cells and their paracrine interactions with the injured brain
Maillacheruvu, P. F., Engel, L. M., Crum, I. T., Agrawal, D. K., & Peeples, E. S. (2017) · Pediatric Research · doi:10.1038/pr.2017.251 · Cited by 9
Blocking of autocrine IGF-1 reduces viability of human umbilical cord mesenchymal stem cells via inhibition of the Akt/Gsk-3β signaling pathway
Wang, Q., Zhang, F., & Hong, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8445 · Cited by 9
“Previous studies indicated that additional supplements of the growth factors, such as insulin-like growth factor 1 (IGF-1), fibroblast growth factor, epidermal growth factor, basic fibroblast growth factor (bFGF) and platelet-derived growth factor may promote the proliferation of MSCs (11-13).”
Insulin-Functionalized Bioactive Fiber Matrices with Bone Marrow-Derived Stem Cells in Rat Achilles Tendon Regeneration
Ramos, D. M., Abdulmalik, S., Arul, M. R., Sardashti, N., Banasavadi‐Siddegowda, Y., Nukavarapu, S. P., Drissi, H., & Kumbar, S. G. (2022) · ACS Applied Bio Materials · doi:10.1021/acsabm.2c00243 · Cited by 8
Prenatal ethanol exposure-induced a low level of foetal blood cholesterol and its mechanism of IGF1-related placental cholesterol transport dysfunction
Zhang, G., Zhou, J., Huang, W. M., Fang, M., Yu, L., Wang, H., & Zhang, Y. (2019) · Toxicology · doi:10.1016/j.tox.2019.152237 · Cited by 8
Efficient and sustained IGF-1 expression in the adipose tissue-derived stem cells mediated via a lentiviral vector
Chen, T., Huang, D., Chen, G., Ting-shu, Y., Yi, J., & Tian, M. (2014) · Journal of Molecular Histology · doi:10.1007/s10735-014-9599-7 · Cited by 8
Remodeling the Th1 polarized systemic environment contributes to neurogenesis and cognitive function via the Wnt7a pathway in neonatal mice
Xu, Y., He, F., Qi, F., Yang, G., Zheng, F., Yang, J., Wang, X., Liu, J., & Zou, J. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.03.002 · Cited by 8
“Accumulating evidence has demonstrated that cross talk between inflammation and Wnt/b-catenin signaling contributes to neurogenesis (Jiang et al., 2015; L’Episcopo et al., 2012).”
Background
Mechanical stretch promotes antioxidant responses and cardiomyogenic differentiation in P19 cells
Cheng, J., Zou, Q., Xue, Y., Sun, C., & Zhang, D. (2021) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.3184 · Cited by 7
“, 2013), trophic factors such as insulin‐ like growth factor‐1, bone morphogenetic protein‐2, and platelet‐ derived growth factors (Beederman et al., 2013; Huat et al., 2014; Li et al., 2014), as well as the extracellular matrix and mechanical cues”
Background
Retracted
Nano-scaffold containing functional motif of stromal cell-derived factor 1 enhances neural stem cell behavior and synaptogenesis in traumatic brain injury
Tork, M. A. B., Saberifar, M., Yekta, H. J., Hajinejad, M., Ravandi, H. H., Gorji, A., & Negah, S. S. (2025) · Scientific Reports · doi:10.1038/s41598-025-85698-5 · Cited by 7
Network-Based Method for Identifying Co-Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues
Chen, L., Pan, H., Zhang, Y., Feng, K., Kong, X., Huang, T., & Cai, Y. (2017) · Genes · doi:10.3390/8100252 · Cited by 7
The role of insulin-like growth factors in modulating the activity of dental mesenchymal stem cells
Bashir, N. Z. (2020) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2020.104993 · Cited by 7
Translational Medicine Strategies in Drug Development for Neurodevelopmental Disorders
Srivastava, S., Şahin, M., & Prock, L. A. (2019) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-803161-2.00022-9 · Cited by 6
Lab-scale Preparation of Recombinant Human Insulin-like Growth Factor-1 in Escherichia coli and its Potential Safety on Normal Human Lung Cell Line
Mohamed, O. A., Samir, S., Omar, H., Hassan, E. A., & Abdelazeem, E. (2022) · Recent Patents on Biotechnology · doi:10.2174/1872208316666220412105822 · Cited by 6
Effect of anthelmintic treatment on serum free IGF-1 and IGFBP-3: a cluster-randomized-controlled trial in Indonesia
Kurniawan, F., Tahapary, D. L., de Ruiter, K., Yunir, E., Biermasz, N. R., Smit, J. W. A., Supali, T., Sartono, E., Yazdanbakhsh, M., & Soewondo, P. (2020) · Scientific Reports · doi:10.1038/s41598-020-75781-4 · Cited by 6
Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans
Wong, T.-H., Chen, T., Tseng, K., Chen, Z.-Y., Chen, C., Lin, F., Wu, H., & Lin, S. (2020) · Aging · doi:10.18632/aging.202166 · Cited by 6
“IGF-I is a mitogen and a mediator of skeletal growth [11, 12].”
Background
MicroRNA expression profile of bone marrow mesenchymal stem cell-derived neural progenitor by microarray under the influence of EGF, bFGF and IGF-1
Huat, T. J., Khan, A. A., Abdullah, J. M., Idris, F. M., & Jaafar, H. (2015) · Genomics Data · doi:10.1016/j.gdata.2015.06.015 · Cited by 6
“Cell culture Primary culture of MSCs was isolated from Sprague Dawley rats' bone marrow tissue by their selective adherence to plastic surface as described previously [2].”
Self-citation
Gelatin Directly Enhances Neurogenic Differentiation Potential in Bone Marrow-Derived Mesenchymal Stem Cells Without Stimulation of Neural Progenitor Cell Proliferation
Lee, H., Han, N. R., Hwang, J. Y., Yun, J. I., Kim, C., Park, K.-H., & Lee, S. T. (2016) · DNA and Cell Biology · doi:10.1089/dna.2016.3237 · Cited by 6
“…et al. , 2015) as chemical compounds, epidermal growth factor (EGF) (Huat et al. , 2014; Mukai et al. , 2016), basic ﬁbroblast growth factor (bFGF) (Huat et al. , 2014; Mukai et al. , 2016), and brain-derived neurotrophic factor (BDNF) (Wang et al. , 2013; Tsai et al. , 2014) as growth factors,…”
Influential
The Challenges of Autologous Cell Therapy: Systemic Anti-thrombotic Therapies Interfering with Serum Coagulation May Disable Autologous Serum-Containing Cell Products for Therapeutical Use
Seeger, F. H., Rasper, T., Bonig, H. B., Aßmus, B., Zeiher, A. M., & Dimmeler, S. (2014) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-014-9584-2 · Cited by 5
Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons
Zhao, X., Han, C., Zeng, Z., Liu, L., Wang, H., Xu, J., Feng, Z., Little, P. J., Quirion, R., & Zheng, W. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/5173184 · Cited by 5
“Insulin-like growth factor 1 receptor (IGF-1R) signaling mediated by IGF-1 is an important pathway for the survival and maintenance of multiple cell types within the central nervous system [12].”
The Effects of miR-22-3p on Differentiation of Human Dental Pulp Stem Cells into Neural Progenitor-Like Cells
Gul, M. T., Khattak, M. N. K., Qaisar, R., Jayakumar, M. N., Samsudin, A. B. R., & Khan, A. A. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04702-1 · Cited by 5
“The differentiation potential of MSCs into NPCs is enhanced with the addition of insulin-like growth factor-1 (IGF-1) [14, 15].”
Self-citation
The Influence of Moringa Oleifera Leaf Powder on Body Weight MYF5 and IGF‐1gene Expression in Japanese Quails
Kurşun, K. (2025) · Veterinary Medicine and Science · doi:10.1002/vms3.70400 · Cited by 4
Transplantation of IGF-1-induced BMSC-derived NPCs promotes tissue repair and motor recovery in a rat spinal cord injury model
Al-Zikri, P. N. H., Huat, T. J., Khan, A. A., Patar, A., Reza, F., Idris, F. M., Abdullah, J. M., & Jaafar, H. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e10384 · Cited by 4
“Differentiation of BMSCs into neural progenitor-like stem cells (NPCs) BMSCs were induced into a neural lineage according to the protocol published previously (Huat et al., 2014).”
BackgroundMethodResultInfluentialSelf-citation
Lactate administration induces skeletal muscle synthesis by influencing Akt/ mTOR and MuRF1 in non‐trained mice but not in trained mice
Kyun, S., Kim, J., Hwang, D., Jang, I., Park, H., & Lim, K. (2024) · Physiological Reports · doi:10.14814/phy2.15952 · Cited by 3
Combined Treatment with Insulin-Like Growth Factor 1 and AMD3100 Improves Motor Outcome in a Murine Model of Neonatal Hypoxic-Ischemic Encephalopathy
Peeples, E. S., Dafferner, A. J., Jiang, J., Lyden, E. R., Punsoni, M., & Agrawal, D. K. (2019) · Developmental Neuroscience · doi:10.1159/000505264 · Cited by 4

Authors: Huat, T. J., Khan, A. A., Pati, S., Mustafa, Z., Abdullah, J. M., & Jaafar, H.
Affiliations: Universiti Sains Malaysia (MY)
Corresponding author: Huat, Tee Jong
ORCID: Huat, Tee Jong
Khan, Amir Ali
Pati, Soumya
Abdullah, Jafri Malin
Jaafar, Hasnan
Venue: BMC Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2014-07-22
Volume: 15
Issue: 1
Pages: 91-91
ISSN: 1471-2202 (ISSN-L)
DOI: 10.1186/1471-2202-15-91
PMC: PMC4117972
OpenAlex: W2045159954
Cited by: 129
References: 29
Citations by year: 2026: 1 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 13 · 2020: 20 · 2019: 13 · 2018: 9 · 2017: 14 · 2016: 14 · 2015: 9 · 2014: 3
FWCI: 6.68
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: BMC Neuroscience (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Greater South Information System
Funders: Universiti Sains Malaysia
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords: insulin-like growth factor I, mesenchymal stem cells, neural progenitor-like cells, neuronal differentiation, cell proliferation, apoptosis, growth factor combination, epidermal growth factor, basic fibroblast growth factor, LiF, brain-derived neurotrophic factor, nestin, neurospheres, neurodegenerative disease treatment
MeSH terms: Animals, Cell Survival, Cells, Cultured, Insulin-Like Growth Factor I, Neuroglia, Neurons, Rats, Sprague-Dawley, Apoptosis, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Neurogenesis, Neural Stem Cells, Mesenchymal Stem Cells, Nestin

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IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells

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