The study of cancer cell in stromal environment through induced pluripotent stem cell-derived mesenchymal stem cells

Jit Kai Loh; Mong Lien Wang; Soon Keng Cheong; Fu Ting Tsai; Shu Huei Huang; Jing Rong Wu; Yi Ping Yang; Shih Hwa Chiou; Alan Han Kiat Ong

doi:10.1097/JCMA.0000000000000759

The study of cancer cell in stromal environment through induced pluripotent stem cell-derived mesenchymal stem cells

Jit Kai Loh, Mong Lien Wang, Soon Keng Cheong, Fu Ting Tsai, Shu Huei Huang, Jing Rong Wu, Yi Ping Yang, Shih Hwa Chiou^*, Alan Han Kiat Ong

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background: The development of mesenchymal stem cells (MSCs) has gained reputation from its therapeutic potential in stem cell regeneration, anti-inflammation, tumor suppression, and drug delivery treatment. Previous studies have shown MSCs have both promoting and suppressing effects against cancer cells. While the limitation of obtaining a large quantity of homologous MSCs for studies and treatment remains a challenge, an alternative approach involving the production of MSCs derived from induced pluripotent stem cells (iPSCs; induced MSCs [iMSCs]) may be a promising prospect given its ability to undergo prolonged passage and with similar therapeutic profiles as that of their MSC counterparts. However, the influence of iMSC in the interaction of cancer cells remains to be explored as such studies are not well established. In this study, we aim to differentiate iPSCs into MSC-like cells as a potential substitute for adult MSCs and evaluate its effect on non-small-cell lung cancer (NSCLC). Methods: iMSCs were derived from iPSCs and validated with reference to the International Society of Cellular Therapy guidelines on MSC criteria. To create a stromal environment, the conditioned medium (CM) of iMSCs was harvested and applied for coculturing of NSCLC of H1975 at different concentrations. The H1975 was then harvested for RNA extraction and subjected to next-generation sequencing (NGS) for analysis. Results: The morphology of iMSCs-CM-treated H1975 was different from an untreated H1975. Our NGS data suggest the occurrence of apoptotic events and the presence of cytokines from H1975's RNA that are treated with iMSCs-CM. Conclusion: Our results have shown that iMSCs may suppress the growth of H1975 by releasing proapoptotic cytokines into coculture media. Using iPSC-derived MSC models allows a deeper study of tumor cross talk between MSC and cancer cells that can be applied for potential future cancer therapy.

Original language	English
Pages (from-to)	821-830
Number of pages	10
Journal	Journal of the Chinese Medical Association
Volume	85
Issue number	8
DOIs	https://doi.org/10.1097/JCMA.0000000000000759
State	Published - 1 Aug 2022

Keywords

Carcinoma, non-small-cell lung
Induced pluripotent stem cells
Mesenchymal stem cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/JCMA.0000000000000759

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@article{b741744e12d744e4ba26e8cf2a148a61,

title = "The study of cancer cell in stromal environment through induced pluripotent stem cell-derived mesenchymal stem cells",

abstract = "Background: The development of mesenchymal stem cells (MSCs) has gained reputation from its therapeutic potential in stem cell regeneration, anti-inflammation, tumor suppression, and drug delivery treatment. Previous studies have shown MSCs have both promoting and suppressing effects against cancer cells. While the limitation of obtaining a large quantity of homologous MSCs for studies and treatment remains a challenge, an alternative approach involving the production of MSCs derived from induced pluripotent stem cells (iPSCs; induced MSCs [iMSCs]) may be a promising prospect given its ability to undergo prolonged passage and with similar therapeutic profiles as that of their MSC counterparts. However, the influence of iMSC in the interaction of cancer cells remains to be explored as such studies are not well established. In this study, we aim to differentiate iPSCs into MSC-like cells as a potential substitute for adult MSCs and evaluate its effect on non-small-cell lung cancer (NSCLC). Methods: iMSCs were derived from iPSCs and validated with reference to the International Society of Cellular Therapy guidelines on MSC criteria. To create a stromal environment, the conditioned medium (CM) of iMSCs was harvested and applied for coculturing of NSCLC of H1975 at different concentrations. The H1975 was then harvested for RNA extraction and subjected to next-generation sequencing (NGS) for analysis. Results: The morphology of iMSCs-CM-treated H1975 was different from an untreated H1975. Our NGS data suggest the occurrence of apoptotic events and the presence of cytokines from H1975's RNA that are treated with iMSCs-CM. Conclusion: Our results have shown that iMSCs may suppress the growth of H1975 by releasing proapoptotic cytokines into coculture media. Using iPSC-derived MSC models allows a deeper study of tumor cross talk between MSC and cancer cells that can be applied for potential future cancer therapy.",

keywords = "Carcinoma, non-small-cell lung, Induced pluripotent stem cells, Mesenchymal stem cells",

author = "Loh, {Jit Kai} and Wang, {Mong Lien} and Cheong, {Soon Keng} and Tsai, {Fu Ting} and Huang, {Shu Huei} and Wu, {Jing Rong} and Yang, {Yi Ping} and Chiou, {Shih Hwa} and Ong, {Alan Han Kiat}",

year = "2022",

month = aug,

day = "1",

doi = "10.1097/JCMA.0000000000000759",

language = "English",

volume = "85",

pages = "821--830",

journal = "Journal of the Chinese Medical Association",

issn = "1726-4901",

publisher = "Elsevier Taiwan LLC",

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}

TY - JOUR

T1 - The study of cancer cell in stromal environment through induced pluripotent stem cell-derived mesenchymal stem cells

AU - Loh, Jit Kai

AU - Wang, Mong Lien

AU - Cheong, Soon Keng

AU - Tsai, Fu Ting

AU - Huang, Shu Huei

AU - Wu, Jing Rong

AU - Yang, Yi Ping

AU - Chiou, Shih Hwa

AU - Ong, Alan Han Kiat

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Background: The development of mesenchymal stem cells (MSCs) has gained reputation from its therapeutic potential in stem cell regeneration, anti-inflammation, tumor suppression, and drug delivery treatment. Previous studies have shown MSCs have both promoting and suppressing effects against cancer cells. While the limitation of obtaining a large quantity of homologous MSCs for studies and treatment remains a challenge, an alternative approach involving the production of MSCs derived from induced pluripotent stem cells (iPSCs; induced MSCs [iMSCs]) may be a promising prospect given its ability to undergo prolonged passage and with similar therapeutic profiles as that of their MSC counterparts. However, the influence of iMSC in the interaction of cancer cells remains to be explored as such studies are not well established. In this study, we aim to differentiate iPSCs into MSC-like cells as a potential substitute for adult MSCs and evaluate its effect on non-small-cell lung cancer (NSCLC). Methods: iMSCs were derived from iPSCs and validated with reference to the International Society of Cellular Therapy guidelines on MSC criteria. To create a stromal environment, the conditioned medium (CM) of iMSCs was harvested and applied for coculturing of NSCLC of H1975 at different concentrations. The H1975 was then harvested for RNA extraction and subjected to next-generation sequencing (NGS) for analysis. Results: The morphology of iMSCs-CM-treated H1975 was different from an untreated H1975. Our NGS data suggest the occurrence of apoptotic events and the presence of cytokines from H1975's RNA that are treated with iMSCs-CM. Conclusion: Our results have shown that iMSCs may suppress the growth of H1975 by releasing proapoptotic cytokines into coculture media. Using iPSC-derived MSC models allows a deeper study of tumor cross talk between MSC and cancer cells that can be applied for potential future cancer therapy.

AB - Background: The development of mesenchymal stem cells (MSCs) has gained reputation from its therapeutic potential in stem cell regeneration, anti-inflammation, tumor suppression, and drug delivery treatment. Previous studies have shown MSCs have both promoting and suppressing effects against cancer cells. While the limitation of obtaining a large quantity of homologous MSCs for studies and treatment remains a challenge, an alternative approach involving the production of MSCs derived from induced pluripotent stem cells (iPSCs; induced MSCs [iMSCs]) may be a promising prospect given its ability to undergo prolonged passage and with similar therapeutic profiles as that of their MSC counterparts. However, the influence of iMSC in the interaction of cancer cells remains to be explored as such studies are not well established. In this study, we aim to differentiate iPSCs into MSC-like cells as a potential substitute for adult MSCs and evaluate its effect on non-small-cell lung cancer (NSCLC). Methods: iMSCs were derived from iPSCs and validated with reference to the International Society of Cellular Therapy guidelines on MSC criteria. To create a stromal environment, the conditioned medium (CM) of iMSCs was harvested and applied for coculturing of NSCLC of H1975 at different concentrations. The H1975 was then harvested for RNA extraction and subjected to next-generation sequencing (NGS) for analysis. Results: The morphology of iMSCs-CM-treated H1975 was different from an untreated H1975. Our NGS data suggest the occurrence of apoptotic events and the presence of cytokines from H1975's RNA that are treated with iMSCs-CM. Conclusion: Our results have shown that iMSCs may suppress the growth of H1975 by releasing proapoptotic cytokines into coculture media. Using iPSC-derived MSC models allows a deeper study of tumor cross talk between MSC and cancer cells that can be applied for potential future cancer therapy.

KW - Carcinoma, non-small-cell lung

KW - Induced pluripotent stem cells

KW - Mesenchymal stem cells

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U2 - 10.1097/JCMA.0000000000000759

DO - 10.1097/JCMA.0000000000000759

M3 - Article

C2 - 35666590

AN - SCOPUS:85136656415

SN - 1726-4901

VL - 85

SP - 821

EP - 830

JO - Journal of the Chinese Medical Association

JF - Journal of the Chinese Medical Association

IS - 8

ER -

The study of cancer cell in stromal environment through induced pluripotent stem cell-derived mesenchymal stem cells

Abstract

Keywords

UN SDGs

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