Current Clinical Application of Mesenchymal Stem Cells in the Treatment of Severe COVID-19 Patients: Review

Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7’ antigen (E7’) as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7’ (ADSC-E7’-eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer.

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Characterization and clinical application of mesenchymal stem cells from equine umbilical cord blood

Journal of Veterinary Science ◽

10.4142/jvs.2013.14.3.367 ◽

2013 ◽

Vol 14 (3) ◽

pp. 367 ◽

Cited By ~ 19

Author(s):

Jun-Gu Kang ◽

Sang-Bum Park ◽

Min-Soo Seo ◽

Hyung-Sik Kim ◽

Joon-Seok Chae ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cord Blood ◽

Umbilical Cord ◽

Clinical Application ◽

Umbilical Cord Blood

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Umbilical Cord Tissue Offers the Greatest Number of Harvestable Mesenchymal Stem Cells for Research and Clinical Application: A Literature Review of Different Harvest Sites

Arthroscopy The Journal of Arthroscopic and Related Surgery ◽

10.1016/j.arthro.2015.03.014 ◽

2015 ◽

Vol 31 (9) ◽

pp. 1836-1843 ◽

Cited By ~ 49

Author(s):

C. Thomas Vangsness ◽

Hal Sternberg ◽

Liam Harris

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Literature Review ◽

Umbilical Cord ◽

Clinical Application ◽

Umbilical Cord Tissue

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Long non-coding RNA HULC affects the proliferation, apoptosis, migration, and invasion of mesenchymal stem cells

Experimental Biology and Medicine ◽

10.1177/1535370218804781 ◽

2018 ◽

Vol 243 (13) ◽

pp. 1074-1082 ◽

Cited By ~ 4

Author(s):

Xiujun Li ◽

Jiali Wang ◽

Yuchen Pan ◽

Yujun Xu ◽

Dan Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Cancer ◽

Clinical Application ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Therapeutic Effects ◽

Non Coding Rna ◽

And Function ◽

Long Non Coding Rna

Further studies on the molecular mechanisms of mesenchymal stem cells in the maintenance of growth and function are essential for their clinical application. Growing evidence has shown that long non-coding RNAs (lncRNAs) play an important role in the regulation of mesenchymal stem cells. Recently, it is reported that highly upregulated in liver cancer (HULC), with another lncRNA MALAT-1, accelerated liver cancer stem cell growth. The regulating role of MALAT-1 in mesenchymal stem cells has been investigated. However, the effects of HULC on the mesenchymal stem cells are unknown. In this study, we overexpressed HULC in mesenchymal stem cells derived from umbilical cord and analyzed the cell phenotypes, proliferation, apoptosis, migration, invasion and differentiation of mesenchymal stem cells. We found that overexpression of HULC significantly promotes cell proliferation through promoting cell division and inhibits cell apoptosis. HULC-overexpressed mesenchymal stem cells migrate and invade faster than control mesenchymal stem cells. HULC has no effect on phenotypes and differentiation of mesenchymal stem cells. Furthermore, we found that the expression of HULC in mesenchymal stem cells could be reduced by several inflammatory factors, including TNF-α, TGF-β1, and R848. Taken together, our data demonstrated that HULC has a vital role in the growth and function maintenance of mesenchymal stem cells without affecting differentiation. Impact statement Exploring the molecular mechanisms of growth and function in MSCs is the key to improve their clinical therapeutic effects. Currently, more and more evidence show that the long non-coding RNA (lncRNA) plays an important role in the growth, stemness and function of MSCs.Both HULC and MALAT1 are the earliest discovered LNCRNAs, which are closely related to tumor growth. All of them can promote the growth of liver cancer stem cells. Previously, we have studied the effects of MALAT1 on the growth and function of MSCs. In this study, we focused on the effects of HULC on MSCs. We elucidated the effects of HULC on the growth and differentiation of MSCs, and explored the relationship between inflammatory stimuli and HULC expression in MSCs. Our findings provide a new molecular target for the growth and clinical application of MSCs.

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