Home Browse Commentary on ‘Surface markers associated with chondrogenic potential...
ALL Metrics
-
Views
-
Downloads
Get PDF
Get XML
Cite
Export
Track
▬
✚
Review

Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’

[version 1; peer review: 3 approved]
Zhihua Lu1,2, Lianqi Yan2, Ming Pei
https://orcid.org/0000-0001-5710-3578
1,3
Zhihua Lu1,2, Lianqi Yan2, Ming Pei
https://orcid.org/0000-0001-5710-3578
1,3
PUBLISHED 23 Jan 2020
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS

Abstract

In the last decade, researchers have searched for predictive surface markers of multipotent mesenchymal stromal/stem cells (MSCs) for ensuring improved therapeutic outcomes following cartilage damage in humans. However, we have achieved only limited progress because of the challenge presented by conflicting data. This commentary provides some evidence to prove a lack of success with current efforts, including an inconsistency in accepted surface markers and chondrogenic potential of MSCs as well as the tissue source–dependent MSC surface markers that correlate with chondrogenic potential. A brief discussion on these disputed topics and perspective about functionally predictive surface markers and standardization of analytic procedures are also highlighted.

Keywords

mesenchymal stromal/stem cell, surface marker, proliferation, chondrogenic differentiation, cartilage

Corresponding author: Ming Pei
Competing interests: No competing interests were disclosed.
Grant information: This work was supported by research grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (award number AR067747-01A1) and the Musculoskeletal Transplant Foundation.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright:  © 2020 Lu Z et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Lu Z, Yan L and Pei M. Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’ [version 1; peer review: 3 approved]. F1000Research 2020, 9(F1000 Faculty Rev):37 (https://doi.org/10.12688/f1000research.21207.1) First published: 23 Jan 2020, 9(F1000 Faculty Rev):37 (https://doi.org/10.12688/f1000research.21207.1) Latest published: 23 Jan 2020, 9(F1000 Faculty Rev):37 (https://doi.org/10.12688/f1000research.21207.1)

Introduction

As a leading cause of disability among adults, osteoarthritis often results from a biochemical breakdown of articular cartilage in joints1. Articular cartilage has a poor intrinsic healing capacity because of its avascular structure, immobility of chondrocytes, and low mitotic activity. Compared with conventional surgical methods, autologous cell therapy, growth factor therapy, and biomaterials provide more promising approaches for clinical treatment2. Human multipotent mesenchymal stromal/stem cell (MSC)-based cell therapy is expected to deliver a promising treatment for cartilage repair because of easy isolation of cells from mesenchymal tissues with higher proliferative and chondrogenic potential3,4. Given that MSCs exist in a number of tissues and organs, such as bone marrow, synovial membrane, and adipose tissue5–7, to compare research outcomes and promote the development of MSC-based therapy, the International Society for Cellular Therapy defined human MSCs in 20068. First, in vitro culture of MSCs must have the ability to adhere to plastic substrates; second, MSCs should express cluster of differentiation 73 (CD73), CD90, and CD105 (>95%), which are measured by flow cytometry. Meanwhile, CD14, CD19, CD34, CD45, and HLA class II should be negative (≤2% positive). Third, MSCs must have osteogenic, chondrogenic, and adipogenic capacities in vitro.

Increasing evidence has shown that human MSC subpopulations which were sorted by some surface markers had better chondrogenic potential for cartilage regeneration. Researchers are trying to find predictive MSC surface markers for ensuring improved therapeutic outcomes. Although some promising MSC surface markers have been comprehensively reviewed9–11, Alegre-Aguarón et al. questioned the correlation between stem cell surface markers and chondrogenic potential12. This commentary provides some evidence to prove a lack of success with current efforts, including an inconsistency in accepted surface markers and chondrogenic potential of MSCs as well as the tissue source–dependent MSC surface markers that correlate with chondrogenic potential. A brief discussion on these disputed topics and perspective about functionally predictive surface markers and standardization of analytic procedures are also highlighted (Figure 1).

ef3eb31d-3bed-4e1e-bc60-4d023bd9bbb8_figure1.gif

Figure 1. Schematic diagram of our Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’.

Human mesenchymal stromal/stem cells (MSCs) were defined in 2006 by the International Society for Cellular Therapy. Unfortunately, currently accepted predictive surface markers do not seem to be ideal candidates to predict MSCs with chondrogenic potential in terms of inconsistency of currently accepted surface markers and chondrogenic potential of MSCs and tissue source–dependent MSC surface markers that correlate with chondrogenic potential. Are functionally predictive surface markers the next target for sorting MSCs in cartilage engineering and regeneration? ∝, positive correlation; ADSC, adipose-derived stromal/stem cell; BMSC, bone marrow-derived stromal/stem cell; dECM, decellularized extracellular matrix; FGF2, fibroblast growth factor 2; LTD EXP, limited expression; NR, not related; SDSC, synovium-derived stromal/stem cell.

Inconsistency of currently accepted surface markers and chondrogenic potential of MSCs

Increasing evidence suggests that environmental preconditioning revitalizes the proliferation and chondrogenic capacity of adult stromal/stem cells13. Given two good examples that decellularized extracellular matrix (dECM) expansion or fibroblast growth factor 2 (FGF2) pretreatment can promote human MSC proliferation and chondrogenic potential, there is an inconsistency in accepted surface markers and chondrogenic potential of MSCs.

dECM expansion

Recent reports demonstrated that dECM deposited by synovium-derived stromal/stem cells (SDSCs) provided an in vitro microenvironment for SDSC expansion, which dramatically improved proliferation and enhanced chondrogenic potential14–16. The flow cytometry data reported by Li et al. showed that, compared with surface markers of human SDSCs grown on tissue culture plastic (TCP), the percentage of CD29, CD90, and CD105 expression of SDSCs grown on dECM decreased slightly but the median fluorescence intensity (MFI) declined dramatically; interestingly, both the percentage and MFI of stage-specific embryonic antigen 4 (SSEA4) increased17. Zhang et al. also found that, despite nearly 100% expression in SDSCs after expansion on either TCP or dECM substrates, CD29, CD90, and CD105 declined dramatically at the MFI in dECM-expanded SDSCs; the MFI of SSEA4 in dECM-expanded cells increased slightly while the percentage doubled18. Interestingly, real-time quantitative polymerase chain reaction results showed that SRY-Box9 (SOX9), type II collagen (COL2A1), and aggrecan (ACAN) were significantly upregulated during chondrogenic induction in SDSCs from the dECM group18. In those two studies, SSEA4 was found to be the only surface marker under evaluation that increased when dECM improved the chondrogenic potential of human SDSCs. However, Li et al. showed that SSEA4(+) expression did not favor human SDSC chondrogenesis because enhanced chondrogenesis occurred in the SSEA4(−) population of cells19.

FGF2 pretreatment

In 2011, Kim et al. found that the expression percentage of surface marker CD49a in human SDSCs decreased with pretreatment using FGF2 and that FGF2 exerted no effect on the expression levels in CD29, CD44, CD73, CD105, and CD16620. In that study, the size, weight, and glycosaminoglycan (GAG) accumulation of pellets increased following FGF2 supplementation during cell expansion. In another study, after seven days of monolayer expansion in the presence of FGF2, human SDSCs became significantly smaller and showed a fibroblast-like appearance as well as a decrease in MFI for CD29, CD90, and CD10; however, FGF2-pretreated SDSCs showed significantly increased chondrogenic potential21. Hagmann et al. reported that FGF2 pretreatment suppressed CD146 expression in human bone marrow–derived stromal/stem cells (BMSCs) and promoted chondrogenic differentiation22. These studies demonstrated that, during ex vivo expansion, FGF2 is an effective agent to promote human MSC proliferation and chondrogenic potential via upregulation of SOX923. However, measured surface markers did not show a positive correlation with the proliferative and chondrogenic potential of MSCs.

Tissue source–dependent MSC surface markers that correlate chondrogenic potential

Some surface markers associated with chondrogenic potential are not equally expressed in all tissue-specific stromal/stem cells. The evidence shown in this section supports the conclusion that the predictive capacity of CD271 and CD105 for MSC chondrogenic potential is tissue source–dependent in terms of MSCs from synovium, bone marrow, and adipose.

CD271

CD271, a low-affinity nerve growth factor receptor, is considered to be a highly selective surface marker for BMSCs24. The reports from Mifune et al.25 and Calabrese et al.26 showed that CD271(+) BMSCs from freshly isolated cells had higher chondrogenic potential as evidenced by increased expression of chondrogenic genes in pellet culture with induction medium compared with CD271(−) BMSCs. Petters et al. demonstrated that, without ex vivo expansion, human bone marrow–derived CD271(+) mononuclear cells could generate sufficient articular cartilage constructs exhibiting high cell viability and remarkable chondrogenic matrix deposition in a type I collagen hydrogel27.

Given that CD271 plays an important predictive role in chondrogenic potential of human BMSCs, there is still controversy over whether human SDSCs express CD27128,29. Some studies reported that CD271 was expressed only in the synovial membrane of patients with osteoarthritis29,30. Interestingly, increasing evidence indicates that SDSCs are tissue-specific stromal/stem cells for chondrogenesis31 and present superior chondrogenic potential and less hypertrophy compared with BMSCs32.

Despite the low abundance of CD271(+) subpopulation within stromal vascular fraction cells, Quirici et al. found that the CD271(+) subpopulation of adipose-derived stromal/stem cells (ADSCs) had high increments in cell proliferation when compared with unsorted ADSCs33. Research by Kohli et al. showed that CD271(+) ADSCs from ex vivo expansion had a superior ability to promote cartilage repair compared with unsorted ADSCs34. However, the study by Beckenkamp et al. showed that, in freshly isolated cells, CD34(+)CD271(+) ADSCs displayed similar in vitro chondrogenic potential at passage 3 compared with CD34(+)CD271(−) ADSCs35.

CD105

CD105 (endoglin) is a transmembrane protein that regulates cellular proliferation, differentiation, and migration36. Cleary et al. found that the percentage of CD105 in human BMSCs was not related to subsequent chondrogenic potential since CD105 expression did not change during cell expansion when chondrogenic potential decreased37. Interestingly, this outcome seems to be inconsistent with the role of CD105 in SDSCs and ADSCs. Arufe et al. in 200938 and Chang et al. in 201339 demonstrated that the cellular subset of CD105(+) SDSCs from ex vivo expansion possessed greater chondrogenic capacity than the CD105(−) SDSC subset. Jiang et al. found that CD105(+) ADSC subpopulation in in vitro culture had a much stronger chondrogenic potential than CD105(−) subpopulation and had more intensive immunostaining of type II collagen and higher gene expression of COL2A1 and ACAN following chondrogenic induction40. There is also a report that myrtucommulone-A treatment reduced CD105 expression in expanded human ADSCs along with reduced chondrogenic potential41.

Discussions and perspectives

In this commentary, we discussed that the same surface markers might perform differently in predicting the chondrogenic potential of MSCs isolated from different tissues. We also highlighted the inconsistency in currently accepted surface markers and chondrogenic potential of MSCs, which brings up the challenge to find more reliable surface markers to meet the demands of future regenerative medicine. A 2017 report from Dickinson et al.42 raised the concept of “functionally predictive surface markers”, which may convey a promising method to address this issue. In the article, the authors used a genomic profiling strategy to find a functional MSC surface marker that can predict enhanced chondrogenic potential. They found that receptor tyrosine kinase-like orphan receptor 2 (ROR2), the Wnt5a receptor, was upregulated in highly chondrogenic clones and used ROR2 to sort the MSC subpopulation which can produce enhanced cartilage constructs with superior efficacy in an animal cartilage repair model. As a functionally predictive surface marker, ROR2 is believed to be important for chondrogenesis, including initial morphology of the cartilage anlagen and subsequent tuning of mature cartilage43, as well as mediating Wnt5a signaling in enhancing chondrogenesis by activation of SOX944. Intriguingly, a recent report from Stüdle et al. did not find human BMSCs to express ROR2 since the percentage of ROR2(+) cells was lower than 0.1%45. The authors also found that high variability both across the donors and across clonally derived strains in BMSCs challenged chondrogenic differentiation outcomes. These results indicate that there is a long way to go to find functionally predictive surface markers for stromal/stem cell–based cartilage engineering and regeneration.

Although many studies have focused on the correlation between human MSC surface markers and chondrogenic potential, there is a lack of standard procedures to quantify surface marker expression. Some procedures might influence the outcome, such as enzyme-dependent cell-detaching methods. A 2017 report compared the effect of cell-detaching methods on the positive proportion of surface markers of cultured SDSCs46. They found that trypsin (catalog number 25200072; Thermo Fisher Scientific, Waltham, WA, USA) obviously reduced the percentage and MFI of CD73(+) cells and CD105(+) cells but had little effect on the percentage of CD90 expression. They also found that TrypLE (catalog number 12563011; Thermo Fisher Scientific) had no influence on the positive proportion of tested surface markers at 30 minutes of digestion but dramatically reduced the CD44(+), CD49c(+), CD73(+), CD140a(+), and CD140b(+) cell populations at 60 minutes of digestion. Collagenase (catalog number C9263; MilliporeSigma, Burlington, MA, USA) was found to reduce the CD58(+), CD105(+), and CD140b(+) cell populations at 120 minutes of digestion. By using flow cytometric analysis, most researchers tend to measure the percentage rather than the MFI of surface markers to assess the influence on MSC chondrogenic potential. However, the percentage analysis method is easily affected by outliers and disregards fluorescent intensity shifts that may show how proliferation and differentiation are progressing by a change in the level of surface marker expression. To overcome the limitations of percentage, Chan et al. proposed an analysis method based on MFI because of its robustness against outliers and increased accuracy47. Therefore, the relationship between surface markers and chondrogenic ability should be further studied by a method including the MFI of MSCs.

Acknowledgments

We thank Suzanne Danley from the Department of Orthopaedics, West Virginia University, for editing the manuscript.

Faculty Opinions recommended

References

  • 1.  Centers for Disease Control and Prevention (CDC): Prevalence of disabilities and associated health conditions among adults--United States, 1999. MMWR Morb Mortal Wkly Rep. 2001; 50(7): 120–5. PubMed Abstract
  • 2.  Falah M, Nierenberg G, Soudry M, et al.: Treatment of articular cartilage lesions of the knee. Int Orthop. 2010; 34(5): 621–30. PubMed Abstract | Publisher Full Text | Free Full Text
  • 3.  Koga H, Engebretsen L, Brinchmann JE, et al.: Mesenchymal stem cell-based therapy for cartilage repair: a review. Knee Surg Sports Traumatol Arthrosc. 2009; 17(11): 1289–97. PubMed Abstract | Publisher Full Text
  • 4.  Pittenger MF, Mackay AM, Beck SC, et al.: Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284(5411): 143–7. PubMed Abstract | Publisher Full Text
  • 5.  Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997; 276(5309): 71–4. PubMed Abstract | Publisher Full Text
  • 6.  De Bari C, Dell'Accio F, Tylzanowski P, et al.: Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001; 44(8): 1928–42. PubMed Abstract | Publisher Full Text
  • 7.  Zuk PA, Zhu M, Ashjian P, et al.: Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002; 13(12): 4279–95. PubMed Abstract | Publisher Full Text | Free Full Text
  • 8.  Dominici M, Le Blanc K, Mueller I, et al.: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4): 315–7. PubMed Abstract | Publisher Full Text | Faculty Opinions Recommendation
  • 9.  Campbell DD, Pei M, et al.: Surface markers for chondrogenic determination: a highlight of synovium-derived stem cells. Cells. 2012; 1(4): 1107–20. PubMed Abstract | Publisher Full Text | Free Full Text
  • 10.  Lv FJ, Tuan RS, Cheung KM, et al.: Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells. 2014; 32(6): 1408–19. PubMed Abstract | Publisher Full Text
  • 11.  Pérez-Silos V, Camacho-Morales A, Fuentes-Mera L: Mesenchymal Stem Cells Subpopulations: Application for Orthopedic Regenerative Medicine. Stem Cells Int. 2016; 2016: 3187491. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 12.  Alegre-Aguarón E, Desportes P, García-Álvarez F, et al.: Differences in surface marker expression and chondrogenic potential among various tissue-derived mesenchymal cells from elderly patients with osteoarthritis. Cells Tissues Organs. 2012; 196(3): 231–40. PubMed Abstract | Publisher Full Text
  • 13.  Pei M: Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential. Biomaterials. 2017; 117: 10–23. PubMed Abstract | Publisher Full Text | Free Full Text
  • 14.  Li J, Pei M: Optimization of an in vitro three-dimensional microenvironment to reprogram synovium-derived stem cells for cartilage tissue engineering. Tissue Eng Part A. 2011; 17(5–6): 703–12. PubMed Abstract | Publisher Full Text
  • 15.  Pei M, He F, Wei L: Three-Dimensional Cell Expansion Substrate for Cartilage Tissue Engineering and Regeneration: A Comparison in Decellularized Matrix Deposited by Synovium-Derived Stem Cells and Chondrocytes. J Tissue Sci Eng. 2011; 2: 104. Publisher Full Text
  • 16.  Pei M, Li JT, Shoukry M, et al.: A review of decellularized stem cell matrix: a novel cell expansion system for cartilage tissue engineering. Eur Cell Mater. 2011; 22: 333–43; discussion 343. PubMed Abstract | Publisher Full Text
  • 17.  Li J, Hansen KC, Zhang Y, et al.: Rejuvenation of chondrogenic potential in a young stem cell microenvironment. Biomaterials. 2014; 35(2): 642–53. PubMed Abstract | Publisher Full Text | Faculty Opinions Recommendation
  • 18.  Zhang Y, Li J, Davis ME, et al.: Delineation of in vitro chondrogenesis of human synovial stem cells following preconditioning using decellularized matrix. Acta Biomater. 2015; 20: 39–50. PubMed Abstract | Publisher Full Text | Free Full Text
  • 19.  Li J, Campbell DD, Bal GK, et al.: Can arthroscopically harvested synovial stem cells be preferentially sorted using stage-specific embryonic antigen 4 antibody for cartilage, bone, and adipose regeneration? Arthroscopy. 2014; 30(3): 352–61. PubMed Abstract | Publisher Full Text
  • 20.  Kim JH, Lee MC, Seong SC, et al.: Enhanced proliferation and chondrogenic differentiation of human synovium-derived stem cells expanded with basic fibroblast growth factor. Tissue Eng Part A. 2011; 17(7–8): 991–1002. PubMed Abstract | Publisher Full Text
  • 21.  Pizzute T, Li J, Zhang Y, et al.: Fibroblast Growth Factor Ligand Dependent Proliferation and Chondrogenic Differentiation of Synovium-Derived Stem Cells and Concomitant Adaptation of Wnt/Mitogen-Activated Protein Kinase Signals. Tissue Eng Part A. 2016; 22(15–16): 1036–46. PubMed Abstract | Publisher Full Text | Free Full Text
  • 22.  Hagmann S, Moradi B, Frank S, et al.: FGF-2 addition during expansion of human bone marrow-derived stromal cells alters MSC surface marker distribution and chondrogenic differentiation potential. Cell Prolif. 2013; 46(4): 396–407. PubMed Abstract | Publisher Full Text
  • 23.  Correa D, Somoza RA, Lin P, et al.: Sequential exposure to fibroblast growth factors (FGF) 2, 9 and 18 enhances hMSC chondrogenic differentiation. Osteoarthritis Cartilage. 2015; 23(3): 443–53. PubMed Abstract | Publisher Full Text | Free Full Text
  • 24.  Álvarez-Viej M, Menéndez-Menéndez Y, Otero-Hernández J: CD271 as a marker to identify mesenchymal stem cells from diverse sources before culture. World J Stem Cells. 2015; 7(2): 470–6. PubMed Abstract | Publisher Full Text | Free Full Text
  • 25.  Mifune Y, Matsumoto T, Murasawa S, et al.: Therapeutic superiority for cartilage repair by CD271-positive marrow stromal cell transplantation. Cell Transplant. 2013; 22(7): 1201–11. PubMed Abstract | Publisher Full Text
  • 26.  Calabrese G, Giuffrida R, Lo Furno D, et al.: Potential Effect of CD271 on Human Mesenchymal Stromal Cell Proliferation and Differentiation. Int J Mol Sci. 2015; 16(7): 15609–24. PubMed Abstract | Publisher Full Text | Free Full Text
  • 27.  Petters O, Schmidt C, Henkelmann R, et al.: Single-Stage Preparation of Human Cartilage Grafts Generated from Bone Marrow-Derived CD271+ Mononuclear Cells. Stem Cells Dev. 2018; 27(8): 545–55. PubMed Abstract | Publisher Full Text | Faculty Opinions Recommendation
  • 28.  Arufe MC, De la Fuente A, Fuentes I, et al.: Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes. J Cell Biochem. 2010; 111(4): 834–45. PubMed Abstract | Publisher Full Text
  • 29.  Karystinou A, Dell'Accio F, Kurth TB, et al.: Distinct mesenchymal progenitor cell subsets in the adult human synovium. Rheumatology (Oxford). 2009; 48(9): 1057–64. PubMed Abstract | Publisher Full Text
  • 30.  Del Rey MJ, Faré R, Usategui A, et al.: CD271+ stromal cells expand in arthritic synovium and exhibit a proinflammatory phenotype. Arthritis Res Ther. 2016; 18: 66. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 31.  Jones BA, Pei M: Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration. Tissue Eng Part B Rev. 2012; 18(4): 301–11. PubMed Abstract | Publisher Full Text
  • 32.  Pizzute T, Lynch K, Pei M: Impact of tissue-specific stem cells on lineage-specific differentiation: a focus on the musculoskeletal system. Stem Cell Rev Rep. 2015; 11(1): 119–32. PubMed Abstract | Publisher Full Text | Free Full Text
  • 33.  Quirici N, Scavullo C, de Girolamo L, et al.: Anti-L-NGFR and -CD34 monoclonal antibodies identify multipotent mesenchymal stem cells in human adipose tissue. Stem Cells Dev. 2010; 19(6): 915–25. PubMed Abstract | Publisher Full Text
  • 34.  Kohli N, Al-Delfi IRT, Snow M, et al.: CD271-selected mesenchymal stem cells from adipose tissue enhance cartilage repair and are less angiogenic than plastic adherent mesenchymal stem cells. Sci Rep. 2019; 9(1): 3194. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 35.  Beckenkamp LR, Souza LEB, Melo FUF, et al.: Comparative characterization of CD271+ and CD271- subpopulations of CD34+ human adipose-derived stromal cells. J Cell Biochem. 2018; 119(5): 3873–84. PubMed Abstract | Publisher Full Text | Faculty Opinions Recommendation
  • 36.  Gonzalez-Garza MT: Adult stem cell membrane markers: their importance and critical role in their proliferation and differentiation potentials. In: Valarmathi MT (Eds.). Stromal cells-structure, function, and therapeutic implications. IntechOpen Limited, London, UK. 2018. Publisher Full Text
  • 37.  Cleary MA, Narcisi R, Focke K, et al.: Expression of CD105 on expanded mesenchymal stem cells does not predict their chondrogenic potential. Osteoarthritis Cartilage. 2016; 24(5): 868–72. PubMed Abstract | Publisher Full Text | Faculty Opinions Recommendation
  • 38.  Arufe MC, De la Fuente A, Fuentes-Boquete I, et al.: Differentiation of synovial CD-105+ human mesenchymal stem cells into chondrocyte-like cells through spheroid formation. J Cell Biochem. 2009; 108(1): 145–55. PubMed Abstract | Publisher Full Text
  • 39.  Chang CB, Han SA, Kim EM, et al.: Chondrogenic potentials of human synovium-derived cells sorted by specific surface markers. Osteoarthritis Cartilage. 2013; 21(1): 190–9. PubMed Abstract | Publisher Full Text
  • 40.  Jiang T, Liu W, Lv X, et al.: Potent in vitro chondrogenesis of CD105 enriched human adipose-derived stem cells. Biomaterials. 2010; 31(13): 3564–71. PubMed Abstract | Publisher Full Text
  • 41.  Izgi K, Sonmez MF, Canatan H, et al.: Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells. Tissue Eng Regen Med. 2017; 14(2): 113–21. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 42.  Dickinson SC, Sutton CA, Brady K, et al.: The Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation. Stem Cells. 2017; 35(11): 2280–91. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 43.  DeChiara TM, Kimble RB, Poueymirou WT, et al.: Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development. Nat Genet. 2000; 24(3): 271–4. PubMed Abstract | Publisher Full Text
  • 44.  Topol L, Jiang X, Choi H, et al.: Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol. 2003; 162(5): 899–908. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 45.  Stüdle C, Occhetta P, Geier F, et al.: Challenges Toward the Identification of Predictive Markers for Human Mesenchymal Stromal Cells Chondrogenic Potential. Stem Cells Transl Med. 2019; 8(2): 194–204. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 46.  Tsuji K, Ojima M, Otabe K, et al.: Effects of Different Cell-Detaching Methods on the Viability and Cell Surface Antigen Expression of Synovial Mesenchymal Stem Cells. Cell Transplant. 2017; 26(6): 1089–102. PubMed Abstract | Publisher Full Text | Free Full Text | Faculty Opinions Recommendation
  • 47.  Chan LY, Yim EK, Choo AB: Normalized median fluorescence: an alternative flow cytometry analysis method for tracking human embryonic stem cell states during differentiation. Tissue Eng Part C Methods. 2013; 19(2): 156–65. PubMed Abstract | Publisher Full Text

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 23 Jan 2020
Comment
Author details Author details
Competing interests
Grant information
Article Versions (1)
Copyright
Download
 
Export To
metrics
Views Downloads
F1000Research - -
PubMed Central
Data from PMC are received and updated monthly.
 - -
Citations
SEE MORE DETAILS
CITE
how to cite this article
Lu Z, Yan L and Pei M. Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’ [version 1; peer review: 3 approved]. F1000Research 2020, 9(F1000 Faculty Rev):37 (https://doi.org/10.12688/f1000research.21207.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
track
receive updates on this article
Track an article to receive email alerts on any updates to this article.

Open Peer Review

Current Reviewer Status: ?
Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 23 Jan 2020
Views
0
Cite
Reviewer Report 23 Jan 2020
Andre J. van Wijnen, Department of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA 
Approved
VIEWS 0
https://doi.org/10.5256/f1000research.23346.r58736
I confirm that I have read this submission and believe that I have an ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
van Wijnen AJ. Reviewer Report For: Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’ [version 1; peer review: 3 approved]. F1000Research 2020, 9(F1000 Faculty Rev):37 (https://doi.org/10.5256/f1000research.23346.r58736)
The direct URL for this report is:
https://f1000research.com/articles/9-37/v1#referee-response-58736
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Report a concern
Views
1
Cite
Reviewer Report 23 Jan 2020
Andrea Barbero, Department of Biomedicine, University Hospital Basel, Basel, Switzerland 
Approved
VIEWS 1
https://doi.org/10.5256/f1000research.23346.r58737
I confirm that I have read this submission and believe that I have an ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Barbero A. Reviewer Report For: Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’ [version 1; peer review: 3 approved]. F1000Research 2020, 9(F1000 Faculty Rev):37 (https://doi.org/10.5256/f1000research.23346.r58737)
The direct URL for this report is:
https://f1000research.com/articles/9-37/v1#referee-response-58737
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Report a concern
Views
1
Cite
Reviewer Report 23 Jan 2020
Gerjo J. V. M. van Osch, Department of Orthopaedics and Department of Otorhinolaryngology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 
Approved
VIEWS 1
https://doi.org/10.5256/f1000research.23346.r58738
I confirm that I have read this submission and believe that I have an ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
van Osch GJVM. Reviewer Report For: Commentary on ‘Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells’ [version 1; peer review: 3 approved]. F1000Research 2020, 9(F1000 Faculty Rev):37 (https://doi.org/10.5256/f1000research.23346.r58738)
The direct URL for this report is:
https://f1000research.com/articles/9-37/v1#referee-response-58738
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Report a concern

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 23 Jan 2020
Comment

Open Peer Review

Reviewer Status

Alongside their report, reviewers assign a status to the article:

Approved
The paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations
A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved
Fundamental flaws in the paper seriously undermine the findings and conclusions

Reviewer Reports

Invited Reviewers
1 2 3
Version 1
23 Jan 20 		read read read
  1. Gerjo J. V. M. van Osch, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  2. Andrea Barbero, University Hospital Basel, Basel, Switzerland
  3. Andre J. van Wijnen, Mayo Clinic, Rochester, USA

Comments on this article

All Comments(0)

Add a comment
Sign up for content alerts

Browse by related subjects

    keyboard_arrow_left Back to all reports
    keyboard_arrow_left Back to all reports
    keyboard_arrow_left Back to all reports
    Alongside their report, reviewers assign a status to the article:
    Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
    Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
    Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
    Sign In
    If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password.

    The email address should be the one you originally registered with F1000.
    Email address not valid, please try again

    You registered with F1000 via Google, so we cannot reset your password.

    To sign in, please click here.

    If you still need help with your Google account password, please click here.

    You registered with F1000 via Facebook, so we cannot reset your password.

    To sign in, please click here.

    If you still need help with your Facebook account password, please click here.

    Code not correct, please try again
    Email us for further assistance.
    Server error, please try again.