Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells
Mesenchymal stem cells from Wharton’s jelly of the human umbilical cord (hWJSCs), and the conditioned medium (hWJSC-CM) prepared from them, were shown to be tumoricidal on many cancers. However, these tumoricidal effects were observed in hWJSCs grown under normoxic conditions of 21% oxygen in the la...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2020/4670948 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832567970799288320 |
|---|---|
| author | Hao Daniel Lin Chui-Yee Fong Arijit Biswas Ariff Bongso |
| author_facet | Hao Daniel Lin Chui-Yee Fong Arijit Biswas Ariff Bongso |
| author_sort | Hao Daniel Lin |
| collection | DOAJ |
| description | Mesenchymal stem cells from Wharton’s jelly of the human umbilical cord (hWJSCs), and the conditioned medium (hWJSC-CM) prepared from them, were shown to be tumoricidal on many cancers. However, these tumoricidal effects were observed in hWJSCs grown under normoxic conditions of 21% oxygen in the laboratory. Since oxygen concentrations in the stem cell niche or physiological microenvironment are hypoxic and help to maintain stemness properties, the objective of this work was to evaluate whether there were differences in the tumoricidal properties of hWJSC-CM grown in 21% O2 (normoxic) or 5% O2 (hypoxic) environments. The results showed that hWJSCs grown under normoxic or hypoxic conditions showed no distinct morphological differences in culture and remained positive in trilineage differentiation into adipocytes, osteocytes, and chondrocytes. Hypoxic hWJSCs expressed the mesenchymal stem cell surface markers CD105, CD90, CD73, CD146, and CD108 similar to normoxic hWJSCs but were negative for the hematopoietic markers CD14, CD19, CD34, CD45, CD117, and HLA-DR. Hypoxic hWJSC-CM produced a significantly greater reduction in cell viability and a significantly greater increase in apoptosis, oxidative stress, and lipid peroxidation in human lymphoma cells compared to normoxic hWJSC-CM. Hypoxic hWJSC-CM also produced significantly greater expression of immunogenic cell death (ICD) hallmarks such as surface-bound calreticulin, HSP70, HSP90, and high mobility group binding 1 proteins and significantly decreased expression of the defense molecules CD47 and PD-L1. This study showed that the tumoricidal effect of hypoxic hWJSC-CM was superior to normoxic hWJSC-CM and should be the preferred choice of preparing hWJSC-CM for the induction of ICD on lymphoma cells. |
| format | Article |
| id | doaj-art-da1effd0ddd044448a705a2fcc49ecfa |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-da1effd0ddd044448a705a2fcc49ecfa2025-02-03T01:00:06ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/46709484670948Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma CellsHao Daniel Lin0Chui-Yee Fong1Arijit Biswas2Ariff Bongso3Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 119228, SingaporeDepartment of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 119228, SingaporeDepartment of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 119228, SingaporeDepartment of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 119228, SingaporeMesenchymal stem cells from Wharton’s jelly of the human umbilical cord (hWJSCs), and the conditioned medium (hWJSC-CM) prepared from them, were shown to be tumoricidal on many cancers. However, these tumoricidal effects were observed in hWJSCs grown under normoxic conditions of 21% oxygen in the laboratory. Since oxygen concentrations in the stem cell niche or physiological microenvironment are hypoxic and help to maintain stemness properties, the objective of this work was to evaluate whether there were differences in the tumoricidal properties of hWJSC-CM grown in 21% O2 (normoxic) or 5% O2 (hypoxic) environments. The results showed that hWJSCs grown under normoxic or hypoxic conditions showed no distinct morphological differences in culture and remained positive in trilineage differentiation into adipocytes, osteocytes, and chondrocytes. Hypoxic hWJSCs expressed the mesenchymal stem cell surface markers CD105, CD90, CD73, CD146, and CD108 similar to normoxic hWJSCs but were negative for the hematopoietic markers CD14, CD19, CD34, CD45, CD117, and HLA-DR. Hypoxic hWJSC-CM produced a significantly greater reduction in cell viability and a significantly greater increase in apoptosis, oxidative stress, and lipid peroxidation in human lymphoma cells compared to normoxic hWJSC-CM. Hypoxic hWJSC-CM also produced significantly greater expression of immunogenic cell death (ICD) hallmarks such as surface-bound calreticulin, HSP70, HSP90, and high mobility group binding 1 proteins and significantly decreased expression of the defense molecules CD47 and PD-L1. This study showed that the tumoricidal effect of hypoxic hWJSC-CM was superior to normoxic hWJSC-CM and should be the preferred choice of preparing hWJSC-CM for the induction of ICD on lymphoma cells.http://dx.doi.org/10.1155/2020/4670948 |
| spellingShingle | Hao Daniel Lin Chui-Yee Fong Arijit Biswas Ariff Bongso Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells Stem Cells International |
| title | Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells |
| title_full | Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells |
| title_fullStr | Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells |
| title_full_unstemmed | Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells |
| title_short | Hypoxic Wharton’s Jelly Stem Cell Conditioned Medium Induces Immunogenic Cell Death in Lymphoma Cells |
| title_sort | hypoxic wharton s jelly stem cell conditioned medium induces immunogenic cell death in lymphoma cells |
| url | http://dx.doi.org/10.1155/2020/4670948 |
| work_keys_str_mv | AT haodaniellin hypoxicwhartonsjellystemcellconditionedmediuminducesimmunogeniccelldeathinlymphomacells AT chuiyeefong hypoxicwhartonsjellystemcellconditionedmediuminducesimmunogeniccelldeathinlymphomacells AT arijitbiswas hypoxicwhartonsjellystemcellconditionedmediuminducesimmunogeniccelldeathinlymphomacells AT ariffbongso hypoxicwhartonsjellystemcellconditionedmediuminducesimmunogeniccelldeathinlymphomacells |