Aim: Variations in the clinical outcomes using mesenchymal stem cells (MSCs) treatments exist, reflecting different origins and niches. To date, there is no consensus on the best source of MSCs most suitable to treat a specific disease. Methods: Total transcriptome analysis of human MSCs was performed. MSCs were isolated from two adult sources bone marrow, adipose tissue and two perinatal sources umbilical cord and placenta. Results: Each MSCs type possessed a unique expression pattern that reflects an advantage in terms of their potential therapeutic use. Advantages in immune modulation, neurogenesis and other aspects were found. Discussion: This study is a milestone for evidence-based choice of the type of MSCs used in the treatment of diseases.

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References

1 Wei X, Yang X, Han Z-P, Qu F-F, Shao L, Shi Y-F. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol. Sin. 34(6), 747 (2013).
Medline CASGoogle Scholar
2 Lee OK, Kuo TK, Chen W-M, Lee K-D, Hsieh S-L, Chen T-H. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103(5), 1669–1675 (2004).
Medline CASGoogle Scholar
3 De Coppi P, Bartsch G Jr, Siddiqui MM et al. Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 25(1), 100 (2007).
Medline CASGoogle Scholar
4 Francis MP, Sachs PC, Elmore LW, Holt SE. Isolating adipose-derived mesenchymal stem cells from lipoaspirate blood and saline fraction. Organogenesis 6(1), 11–14 (2010).
MedlineGoogle Scholar
5 Prockop DJ, Oh JY. Medical therapies with adult stem/progenitor cells (MSCs): a backward journey from dramatic results in vivo to the cellular and molecular explanations. J. Cell. Biochem. 113(5), 1460–1469 (2012).
Medline CASGoogle Scholar
6 Watson N, Divers R, Kedar R et al. Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells. Cytotherapy 17(1), 18–24 (2015).
MedlineGoogle Scholar
7 Gao LR, Zhang NK, Ding QA et al. Common expression of stemness molecular markers and early cardiac transcription factors in human Wharton's jelly-derived mesenchymal stem cells and embryonic stem cells. Cell Transplant. 22(10), 1883–1900 (2013).
MedlineGoogle Scholar
8 Nekanti U, Rao VB, Bahirvani AG, Jan M, Totey S, Ta M. Long-term expansion and pluripotent marker array analysis of Wharton's jelly-derived mesenchymal stem cells. Stem Cells Dev. 19(1), 117–130 (2010).
Medline CASGoogle Scholar
9 Yu S, Long J, Yu J et al. Analysis of differentiation potentials and gene expression profiles of mesenchymal stem cells derived from periodontal ligament and Wharton's jelly of the umbilical cord. Cells Tissues Organs 197(3), 209–223 (2013).
Medline CASGoogle Scholar
10 Fong C-Y, Chak L-L, Biswas A et al. Human Wharton's jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev. 7(1), 1–16 (2011).
Medline CASGoogle Scholar
11 Secco M, Moreira YB, Zucconi E et al. Gene expression profile of mesenchymal stem cells from paired umbilical cord units: cord is different from blood. Stem Cell Rev. 5(4), 387–401 (2009).
Medline CASGoogle Scholar
12 Tsai MS, Hwang SM, Chen KD et al. Functional network analysis of the transcriptomes of mesenchymal stem cells derived from amniotic fluid, amniotic membrane, cord blood, and bone marrow. Stem Cells 25(10), 2511–2523 (2007).
Medline CASGoogle Scholar
13 Al-Najar M, Khalil H, Al-Ajlouni J et al. Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a Phase I/II study. J. Orthop. Surg. 12(1), 190 (2017).
Google Scholar
14 Pandamooz S, Hadipour A, Akhavan-Niaki H et al. Short exposure to collagenase and coculture with mouse embryonic pancreas improve human dermal fibroblast culture. Biotechnol. Appl. Biochem. 59(3), 254–261 (2012).
Medline CASGoogle Scholar
15 Feng B, Jiang J, Kraus P et al. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat. Cell Biol. 11(2), 197 (2009).
Medline CASGoogle Scholar
16 Nichols T, Hayasaka S. Controlling the familywise error rate in functional neuroimaging: a comparative review. Stat. Methods Med. Res. 12(5), 419–446 (2003).
MedlineGoogle Scholar
17 Subramanian A, Tamayo P, Mootha VK et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102(43), 15545–15550 (2005).
Medline CASGoogle Scholar
18 Kolle G, Ho M, Zhou Q et al. Identification of human embryonic stem cell surface markers by combined membrane-polysome translation state array analysis and immunotranscriptional profiling. Stem Cells 27(10), 2446–2456 (2009).
Medline CASGoogle Scholar
19 Gedye CA, Hussain A, Paterson J et al. Cell surface profiling using high-throughput flow cytometry: a platform for biomarker discovery and analysis of cellular heterogeneity. PLoS ONE 9(8), e105602 (2014).
MedlineGoogle Scholar
20 Roson-Burgo B, Sanchez-Guijo F, Del Cañizo C, De Las Rivas J. Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling. BMC Genomics 17(1), 944 (2016).
MedlineGoogle Scholar
21 Heo JS, Choi Y, Kim H-S, Kim HO. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue. Int. J. Mol. Med. 37(1), 115–125 (2016).
MedlineGoogle Scholar
22 Jääger K, Islam S, Zajac P, Linnarsson S, Neuman T. RNA-seq analysis reveals different dynamics of differentiation of human dermis-and adipose-derived stromal stem cells. PLoS ONE 7(6), e38833 (2012).
Medline CASGoogle Scholar
23 Lorenz K, Sicker M, Schmelzer E et al. Multilineage differentiation potential of human dermal skin-derived fibroblasts. Exp. Dermatol. 17(11), 925–932 (2008).
Medline CASGoogle Scholar
24 Burnouf T, Strunk D, Koh MB, Schallmoser KJB. Human platelet lysate: replacing fetal bovine serum as a gold standard for human cell propagation? Biomaterials 76, 371–387 (2016).
Medline CASGoogle Scholar
25 Doucet C, Ernou I, Zhang Y et al. Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J. Cell. Physiol. 205(2), 228–236 (2005).
Medline CASGoogle Scholar
26 Flemming A, Schallmoser K, Strunk D, Stolk M, Volk H-D, Seifert M. Immunomodulative efficacy of bone marrow-derived mesenchymal stem cells cultured in human platelet lysate. J. Clin. Immunol. 31(6), 1143–1156 (2011).
MedlineGoogle Scholar
27 Becherucci V, Piccini L, Casamassima S et al. Human platelet lysate in mesenchymal stromal cell expansion according to a GMP grade protocol: a cell factory experience. Stem Cell. Res. Ther. 9(1), 124 (2018).
Medline CASGoogle Scholar
28 Siegel G, Kluba T, Hermanutz-Klein U, Bieback K, Northoff H, Schäfer R. Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells. BMC Med. 11(1), 146 (2013).
Medline CASGoogle Scholar
29 Buyl K, Vanhaecke T, Desmae T et al. Evaluation of a new standardized enzymatic isolation protocol for human umbilical cord-derived stem cells. Toxicol. In Vitro 29(6), 1254–1262 (2015).
Medline CASGoogle Scholar
30 Seifert A, Werheid DF, Knapp SM, Tobiasch E. Role of Hox genes in stem cell differentiation. World J. Stem Cells 7(3), 583 (2015).
MedlineGoogle Scholar
31 Yang HJ, Xia YY, Wang L et al. A novel role for neural cell adhesion molecule in modulating insulin signaling and adipocyte differentiation of mouse mesenchymal stem cells. J. Cell Sci. 124(pt 15), 2552–2560 (2011).
MedlineGoogle Scholar
32 Kessenbrock K, Wang C-Y, Werb Z. Matrix metalloproteinases in stem cell regulation and cancer. Matrix Biol. 44, 184–190 (2015).
MedlineGoogle Scholar
33 Klein G, Schmal O, Aicher WK. Matrix metalloproteinases in stem cell mobilization. Matrix Biol. 44, 175–183 (2015).
MedlineGoogle Scholar
34 Lee RH, Kim B, Choi I et al. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell. Physiol. Biochem. 14(4–6), 311–324 (2004).
Medline CASGoogle Scholar
35 Prall WC, Czibere A, Jager M et al. Age-related transcription levels of KU70, MGST1 and BIK in CD34⁺ hematopoietic stem and progenitor cells. Mech. Ageing Dev. 128(9), 503–510 (2007).
Medline CASGoogle Scholar
36 Hart ML, Rusch E, Kaupp M, Nieselt K, Aicher WK. Expression of Desmoglein 2, Desmocollin 3 and Plakophilin 2 in placenta and bone marrow-derived mesenchymal stromal cells. Stem Cell Rev. 13(2), 258–266 (2017).
Medline CASGoogle Scholar
37 Thaci B, Brown CE, Binello E, Werbaneth K, Sampath P, Sengupta S. Significance of interleukin-13 receptor α 2-targeted glioblastoma therapy. Neuro-Oncol. 16(10), 1304–1312 (2014).
Medline CASGoogle Scholar
38 Shukla S, MacLennan GT, Hartman DJ, Fu P, Resnick MI, Gupta S. Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int. J. Cancer 121(7), 1424–1432 (2007).
Medline CASGoogle Scholar
39 Karaöz E, Demircan PÇ, Erman G, Güngörürler E, Sarıboyacı AE. Comparative analyses of immunosuppressive characteristics of bone-marrow, Wharton's Jelly, and adipose tissue-derived human mesenchymal stem cells. Turk. J. Hematol. 34(3), 213 (2017).
Medline CASGoogle Scholar
40 Wang Q, Yang Q, Wang Z et al. Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton's jelly as sources of cell immunomodulatory therapy. Hum. Vaccin. Immunother. 12(1), 85–96 (2016).
MedlineGoogle Scholar
41 Li X, Bai J, Ji X, Li R, Xuan Y, Wang Y. Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation. Int. J. Mol. Med. 34(3), 695–704 (2014).
MedlineGoogle Scholar
42 Ghosh AK, Sinha D, Mukherjee S, Biswas R, Biswas T. LPS stimulates and Hsp70 down-regulates TLR4 to orchestrate differential cytokine response of culture-differentiated innate memory CD8(⁺) T cells. Cytokine 73(1), 44–52 (2015).
Medline CASGoogle Scholar
43 Rashedi I, Gomez-Aristizabal A, Wang XH, Viswanathan S, Keating A. TLR3 or TLR4 activation enhances mesenchymal stromal cell-mediated Treg induction via notch signaling. Stem Cells 35(1), 265–275 (2017).
Medline CASGoogle Scholar
44 Nemoto Y, Kanai T, Takahara M et al. Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells. Gut 62(8), 1142–1152 (2013).
Medline CASGoogle Scholar
45 Fong CY, Chak LL, Biswas A et al. Human Wharton's jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev. 7(1), 1–16 (2011).
Medline CASGoogle Scholar
46 Amouzegar A, Mittal SK, Sahu A, Sahu SK, Chauhan SK. Mesenchymal stem cells modulate differentiation of myeloid progenitor cells during inflammation. Stem Cells 35(6), 1532–1541 (2017).
Medline CASGoogle Scholar
47 Pietilä M, Lehtonen S, Tuovinen E et al. CD200 positive human mesenchymal stem cells suppress TNF-α secretion from CD200 receptor positive macrophage-like cells. PLoS ONE 7(2), e31671 (2012).
Medline CASGoogle Scholar
48 Cho K-A, Park M, Kim Y-H, Woo S-Y, Ryu K-H. RNA sequencing reveals a transcriptomic portrait of human mesenchymal stem cells from bone marrow, adipose tissue, and palatine tonsils. Sci. Rep. 7(1), 17114 (2017).
MedlineGoogle Scholar
49 Fitzsimmons RE, Mazurek MS, Soos A, Simmons CA. Mesenchymal stromal/stem cells in regenerative medicine and tissue engineering. Stem Cells Int. (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120267/
MedlineGoogle Scholar
50 Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25(11), 2739–2749 (2007).
Medline CASGoogle Scholar
51 Hopkins A, Mirzayans F, Berry F. Foxc1 expression in early osteogenic differentiation is regulated by BMP4-SMAD activity. J. Cell. Biochem. 117(7), 1707–1717 (2016).
Medline CASGoogle Scholar
52 Mirzayans F, Lavy R, Penner-Chea J, Berry FB. Initiation of early osteoblast differentiation events through the direct transcriptional regulation of Msx2 by FOXC1. PLoS ONE 7(11), e49095 (2012).
Medline CASGoogle Scholar
53 Wu M, Chen G, Li Y-P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Research 4, 16009 (2016).
MedlineGoogle Scholar
54 Sakai K, Kimata K, Sato T et al. Chondroitin sulfate N-acetylgalactosaminyltransferase-1 plays a critical role in chondroitin sulfate synthesis in cartilage. J. Biol. Chem. (2006). www.jbc.org/content/282/6/4152.full.
Google Scholar
55 Hoover DJ, Zhu V, Chen R et al. Expression of the chitinase family glycoprotein YKL-40 in undifferentiated, differentiated and trans-differentiated mesenchymal stem cells. PLoS ONE 8(5), e62491 (2013).
Medline CASGoogle Scholar
56 Johansen JS, Høyer PE, Larsen LA, Price PA, Møllgård K. YKL-40 protein expression in the early developing human musculoskeletal system. J. Histochem. Cytochem. 55(12), 1213–1228 (2007).
Medline CASGoogle Scholar
57 Cleary MA, Van Osch GJM, Brama PA, Hellingman CA, Narcisi R. FGF, TGFβ and Wnt crosstalk: embryonic to in vitro cartilage development from mesenchymal stem cells. J. Tissue Eng. Regen. Med. 9(4), 332–342 (2015).
Medline CASGoogle Scholar
58 Green JD, Tollemar V, Dougherty M et al. Multifaceted signaling regulators of chondrogenesis: implications in cartilage regeneration and tissue engineering. Genes Dis. 2(4), 307–327 (2015).
MedlineGoogle Scholar
59 Oka K, Oka S, Sasaki T et al. The role of TGF-β signaling in regulating chondrogenesis and osteogenesis during mandibular development. Dev. Biol. 303(1), 391–404 (2007).
Medline CASGoogle Scholar
60 Yu L, Liu H, Yan M et al. Shox2 is required for chondrocyte proliferation and maturation in proximal limb skeleton. Dev. Biol. 306(2), 549–559 (2007).
Medline CASGoogle Scholar
61 Akinci B, Meral R, Oral EA. Update on therapeutic options in lipodystrophy. Curr. Diab. Rep. 18(12), 139 (2018).
MedlineGoogle Scholar
62 Nakamura T, Mizuno S. The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine. Proc. Jpn Acad. Ser. B Phys. Biol. Sci. 86(6), 588–610 (2010).
Medline CASGoogle Scholar
63 Rittchen S, Boyd A, Burns A et al. Myelin repair in vivo is increased by targeting oligodendrocyte precursor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF). Biomaterials 56, 78–85 (2015).
Medline CASGoogle Scholar
64 Kang C-M, Kim H, Song JS et al. Genetic comparison of stemness of human umbilical cord and dental pulp. Stem Cells Int. (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819116/
Google Scholar
65 Gao QQ, McNally EM. The dystrophin complex: structure, function, and implications for therapy. Compr. Physiol. 5(3), 1223–1239 (2011).
Google Scholar
66 Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2(12), 731–740 (2003).
Medline CASGoogle Scholar
67 Mizuhashi K, Kanamoto T, Moriishi T et al. Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements. Hum. Mol. Genet. 23(11), 2953–2967 (2014).
Medline CASGoogle Scholar
68 Worzfeld T, Offermanns S. Semaphorins and plexins as therapeutic targets. Nat. Rev. Drug Discov. 13, 603 (2014).
Medline CASGoogle Scholar
69 Polisetti N, Agarwal P, Khan I, Kondaiah P, Sangwan VS, Vemuganti GK. Gene expression profile of epithelial cells and mesenchymal cells derived from limbal explant culture. Mol. Vis. 16, 1227–1240 (2010).
Medline CASGoogle Scholar
70 Roson-Burgo B, Sanchez-Guijo F, Del Cañizo C, De Las Rivas J. Transcriptomic portrait of human mesenchymal stromal/stem cells isolated from bone marrow and placenta. BMC Genomics 15(1), 910 (2014).
MedlineGoogle Scholar
71 Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nat. Rev. Mol. Cell Biol. 10(2), 116 (2009).
Medline CASGoogle Scholar
72 Heinrich E-M, Dimmeler S. MicroRNAs and stem cells: control of pluripotency, reprogramming, and lineage commitment. Circ. Res. 110(7), 1014–1022 (2012).
Medline CASGoogle Scholar
73 Raza U, Saatci Ö, Uhlmann S et al. The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelial–mesenchymal transition in breast cancer. Oncotarget 7(31), 49859 (2016).
MedlineGoogle Scholar
74 Zhang J-X, Chen Z-H, Xu Y et al. Downregulation of microRNA-644a promotes esophageal squamous cell carcinoma aggressiveness and stem cell–like phenotype via dysregulation of PITX2. Clin. Cancer Res. 23(1), 298–310 (2017).
Medline CASGoogle Scholar
75 Liang T, Guo L, Liu C. Genome-wide analysis of mir-548 gene family reveals evolutionary and functional implications. Biomed. Res. Int. (2012). www.hindawi.com/journals/bmri/2012/679563/.
Google Scholar
76 Jasinski-Bergner S, Reches A, Stoehr C et al. Identification of novel microRNAs regulating HLA-G expression and investigating their clinical relevance in renal cell carcinoma. Oncotarget 7(18), 26866–26878 (2016).
MedlineGoogle Scholar
77 Sun Y, Yang Z, Zheng B et al. A novel regulatory mechanism of smooth muscle α-actin expression by NRG-1/circACTA2/miR-548f-5p axis. Circ. Res. 121(6), 628–635 (2017).
Medline CASGoogle Scholar

Vol. 14, No. 9

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Received 23 October 2018

Accepted 15 January 2019

Published online 31 January 2019

Published in print September 2019

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.futuremedicine.com/doi/suppl/10.2217/rme-2018-0137

Acknowledgments

The authors thank L Amaireh (Cell Therapy Center, Jordan) for her assistance in the design of the graphical abstract. The authors thank M Ighnaim (Green Vision, Jordan) for his technical support. The authors are grateful to H Jafar for her administrative help.

Financial & competing interests disclosure

This work was supported by Scientific Research Fund/Ministry of Higher Education/Amman/Jordan, grant number MPH/1/41/2015. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval (Cell Therapy Center/The University of Jordan) and have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations.

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