Letter for the article Hypoxia Effects in Intervertebral Disc Derived

Dear editor

We thank the authors who reported their research in Hypoxia Effects in Intervertebral Disc-Derived Stem Cells and Discus Secretomes: An in vitro Study, published in Stem Cells and Cloning: Advances and Applications 2022;15:21-28. This is very important information on hypoxic preconditioning in mesenchymal stem cells/MSC for therapy of degenerative diseases.1

In this study, the authors reported that 3% oxygen (O2) levels could increase secretion of growth factors, particularly fibroblast growth factor/FGF and platelet growth factor/PDGF, while increased secretion of transforming growth factor/TGF-β1 required higher oxygen levels (5%). These results suggested that MSC might secrete different growth factors depending on environmental conditions, including oxygen levels or hypoxic preconditioning. That means that o2 Levels can allow MSC to produce growth factors for specific purposes. For example, TGF-β1 acted as an immunosuppressant to overcome inflammation and speed up cell regeneration.2 However, if the experimental goal was to increase cell proliferation, which is strongly influenced by FGF and PDGF, then hypoxia 3% O2 is recommended.

Stem cells in this study were isolated from disc stem cells/IVDS. Currently, many researchers are interested in the potential of IVDS to address the problem of disc degeneration. Unfortunately, this study did not report their stem cell characterization, so we could not accurately estimate the purity of stem cells in the cell population. Stem cell characterization could provide information about the type of stem cells that produced these growth factors (FGF, PDGF, VEGF and TGF-β1).

Other studies have reported that secretion of cytokines and growth factors by MSCs derived from gums, adipose tissue, umbilical cord, or Wharton’s jelly tend to increase in a hypoxic microenvironment.3-5 Upregulation of pro-inflammatory and anti-inflammatory cytokines and chemokines can certainly be used as immunomodulators.5 Elevated neurotrophic factor would be very beneficial for nerve cell regeneration.3

More information on the sources of stem cells and the methods to obtain the secretome containing cytokines, chemokines and growth factors would be very useful as evidence for translational research from in vitro and preclinical research towards clinical trials.


we want dr Thank Sunarno for his suggestions and advice, we also appreciate all the support given to the authors during the writing of the article.


The authors report no conflicts of interest in this communication.


1. Romaniyanto MF, Prakoeswa CRS, Notobroto HB, et al. Hypoxia effects in disc stem cells and disc secretomes: an in vitro study. Stem cell cloning Adv Appl. 2022;15:21-28. doi:10.2147/SCCAA.S363951

2. Bavarsad SS, Jalali MT, Nejad DB, Alypoor B, Rezaei HB, Mohammadtaghvaei N. TGFβ1-pretreated Wharton jelly mesenchymal stem cell exosomes as a therapeutic strategy to ameliorate liver fibrosis. Hepat Mon. 2022;22(1):1-12. doi:10.5812/hepatmon-123416

3. Patil S, Fageeh HN, Fageeh HI, et al. Hypoxia, a dynamic tool to enhance the potential of gingival mesenchymal stem cells to secrete neurotrophic factors. Saudi J. Biol. Sci. 2022;29(5):3568-3576. doi:10.1016/j.sjbs.2022.02.039

4. Laksmitawati DR, Widowati W, Noverina R, et al. Production of inflammatory mediators in conditioned medium from adipose-derived mesenchymal stem cells (ATMSC)-treated fresh frozen plasma. Med Sci Monitor Basic Res. 2022;28:e933726. doi:10.12659/msmbr.933726

5. Chouw A, Sartika CR, Milanda T, Faried A. Interleukin profiling in mesenchymal stem cell-derived umbilical cord secretomes. Stem cell cloning Adv Appl. 2022;15:1-9. doi:10.2147/SCCAA.S356763

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