CoChat
Sign Up
PreprintCited by 17Mesenchymal stem cell researchBone Tissue Engineering MaterialsPeriodontal Regeneration and Treatments

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

DONOR VARIABILITY IN HUMAN MESENCHYMAL STEM CELL OSTEOGENIC RESPONSE AS A FUNCTION OF PASSAGE CONDITIONS AND DONOR SEX

Open access
Kolliopoulos, Vasiliki, Tiffany, Aleczandria, Polanek, Maxwell, Harley, Brendan A.C.·2023·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2023.11.12.566781PMC PMC10680622
Open this paper in CoChat — free accountOpen PDF

Abstract

Contemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their potential to differentiate to various tissue-specific cells and generate a pro-regenerative secretome. While MSC differentiation and therapeutic potential can differ as a function of matrix environment, it may also be widely influenced as a function of donor-to-donor variability. Further, effects of passage number and donor sex may further convolute the identification of clinically effective MSC-mediated regeneration technologies. We report efforts to adapt a well-defined mineralized collagen scaffold platform to study the influence of MSC proliferation and osteogenic potential as a function of passage number and donor sex. Mineralized collagen scaffolds broadly support MSC osteogenic differentiation and regenerative potency in the absence of traditional osteogenic supplements for a wide range of MSCs (rabbit, rat, porcine, human). We obtained a library of bone marrow and adipose tissue derived stem cells to examine donor-variability of regenerative potency in mineralized collagen scaffolds. MSCs displayed reduced proliferative capacity as a function of passage duration. Further, MSCs showed significant sex-based differences. Notably, MSCs from male donors displayed significantly higher metabolic activity and proliferation while MSCs from female donor displayed significantly higher osteogenic response via increased alkaline phosphate activity, osteoprotegerin release, and mineral formation in vitro. Our study highlights the essentiality of considering MSC donor sex and culture expansion in future studies of biomaterial regenerative potential.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2023.11.12.566781

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1: Experimental design and overview. (A) Experimental overview for passage scheme study. Human mesenchymal stem cells (hMSCs) from 4 donors (2 male, 2 female) were cultured on mineralized collagen scaffolds after varying passage schemes to compare the influence of passage number and culture length on cell proliferation and response. hMSCs were thawed at passage 3 and seeded at passage 6 (p3–6) undergoing 2 passages in culture prior to being seeded on mineralized collagen scaffolds. hMSCs were thawed at passage 3 and seeded at passage 5 (p3–5) undergoing 1 passage in culture prior to being seeded on mineralized collagen scaffolds. hMSCs were thawed at passage 4 and seeded at passage 5 (p4–5) undergoing 1 passage in culture prior to being seeded on mineralized collagen scaffolds. These cells were subsequently cultured for 21 days and their metabolic activity, cell proliferation and secretome were quantified. (B) Experimental overview for donor variability study. hMSCs from 8 donors (4 male, 4 female) were cultured as p3–5 or p4–5 groups and cultured on mineralized collagen scaffolds for 56 days. Cell response on these scaffolds was quantified to identify donor and sex-based differences.
Figure 1: Experimental design and overview. (A) Experimental overview for passage scheme study. Human mesenchymal stem cells (hMSCs) from 4 donors (2 male, 2 female) were cultured on mineralized collagen scaffolds after varying passage schemes to compare the influence of passage number and culture length on cell proliferation and response. hMSCs were thawed at passage 3 and seeded at passage 6 (p3–6) undergoing 2 passages in culture prior to being seeded on mineralized collagen scaffolds. hMSCs were thawed at passage 3 and seeded at passage 5 (p3–5) undergoing 1 passage in culture prior to being seeded on mineralized collagen scaffolds. hMSCs were thawed at passage 4 and seeded at passage 5 (p4–5) undergoing 1 passage in culture prior to being seeded on mineralized collagen scaffolds. These cells were subsequently cultured for 21 days and their metabolic activity, cell proliferation and secretome were quantified. (B) Experimental overview for donor variability study. hMSCs from 8 donors (4 male, 4 female) were cultured as p3–5 or p4–5 groups and cultured on mineralized collagen scaffolds for 56 days. Cell response on these scaffolds was quantified to identify donor and sex-based differences.CC BY-ND · PubMed Central
Figure 2: Passage scheme influences on metabolic activity, cell number, soluble factor secretion, and ALP activity. Four donors (B, G – male, and C, F – female) with three passage methods (p3–5, p3–6, and p4–5) were cultured on mineralized collagen scaffolds for 21-days. (A) Metabolic activity was quantified via alamarBlue and decreases over time for all donors. The effect of passage scheme on metabolic activity is donor dependent. (B) Cell number was quantified via DNA extraction and remains relatively constant for all donors. The effect of passage scheme on cell number is donor dependent. (C) Secreted osteoprotegerin (OPG) was quantified using an ELISA and increases over 21 days in culture for all donors. Secretion is significantly different between passages at all timepoints for all donors except Donor B. (D) Alkaline phosphatase (ALP) activity was quantified using an ALP activity kit and increases over the 21 days of culture for all donors. ALP activity is significantly different for all donors beginning at Day 9. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value).
Figure 2: Passage scheme influences on metabolic activity, cell number, soluble factor secretion, and ALP activity. Four donors (B, G – male, and C, F – female) with three passage methods (p3–5, p3–6, and p4–5) were cultured on mineralized collagen scaffolds for 21-days. (A) Metabolic activity was quantified via alamarBlue and decreases over time for all donors. The effect of passage scheme on metabolic activity is donor dependent. (B) Cell number was quantified via DNA extraction and remains relatively constant for all donors. The effect of passage scheme on cell number is donor dependent. (C) Secreted osteoprotegerin (OPG) was quantified using an ELISA and increases over 21 days in culture for all donors. Secretion is significantly different between passages at all timepoints for all donors except Donor B. (D) Alkaline phosphatase (ALP) activity was quantified using an ALP activity kit and increases over the 21 days of culture for all donors. ALP activity is significantly different for all donors beginning at Day 9. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value).CC BY-ND · PubMed Central
Figure 3: Donor variability influence on metabolic activity and cell number. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. Metabolic activity and cell number were quantified over the course of the experiment. (A, B) Metabolic activity was quantified via alamarBlue. Male cells are more metabolically active than female cells in both passage schemes. (C, D) Cell number was quantified via DNA extraction. Male cells are more proliferative than female cells in both passage schemes. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value). Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint.
Figure 3: Donor variability influence on metabolic activity and cell number. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. Metabolic activity and cell number were quantified over the course of the experiment. (A, B) Metabolic activity was quantified via alamarBlue. Male cells are more metabolically active than female cells in both passage schemes. (C, D) Cell number was quantified via DNA extraction. Male cells are more proliferative than female cells in both passage schemes. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value). Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint.CC BY-ND · PubMed Central
Figure 4: Donor variability influence on osteoprotegerin secretion and alkaline phosphatase activity. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. (A, B) Osteoprotegerin (OPG) was quantified via ELISA. There were no significant sex differences in OPG secretion for either passage scheme. (C, D) Alkaline phosphatase (ALP) activity was quantified using an ALP activity assay. Female cells have significantly higher ALP activity than male cells in p4–5. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value). Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint.
Figure 4: Donor variability influence on osteoprotegerin secretion and alkaline phosphatase activity. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. (A, B) Osteoprotegerin (OPG) was quantified via ELISA. There were no significant sex differences in OPG secretion for either passage scheme. (C, D) Alkaline phosphatase (ALP) activity was quantified using an ALP activity assay. Female cells have significantly higher ALP activity than male cells in p4–5. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value). Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint.CC BY-ND · PubMed Central
Figure 5: Donor variability influence on calcium and phosphorus content in mineralized collagen scaffolds. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. Mineral content was quantified at Day 56. Cell-seeded scaffolds are compared to unseeded control scaffolds that underwent all media changes throughout the 56-day culture period. (A, B) Calcium content at Day 56 was quantified using inductively couple plasma mass spectrometry (ICP-MS). Female cells have higher calcium content than male cells in p4–5. (C, D) Phosphorous content was quantified using ICP-MS. Female cells have higher phosphorus content than male ells in p4–5. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value). Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint.
Figure 5: Donor variability influence on calcium and phosphorus content in mineralized collagen scaffolds. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. Mineral content was quantified at Day 56. Cell-seeded scaffolds are compared to unseeded control scaffolds that underwent all media changes throughout the 56-day culture period. (A, B) Calcium content at Day 56 was quantified using inductively couple plasma mass spectrometry (ICP-MS). Female cells have higher calcium content than male cells in p4–5. (C, D) Phosphorous content was quantified using ICP-MS. Female cells have higher phosphorus content than male ells in p4–5. Groups that share a letter are not significantly different (p<0.05). Alphabetical order indicates magnitude (i.e., group labeled a has the highest experimental value). Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint.CC BY-ND · PubMed Central
Figure 6: Gene expression analysis at Day 56 of culture. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. A custom Nanostring gene expression panel was used to quantify gene expression over the course of the experiment. (A) Male cells have higher expression of osteogenic genes in both passage schemes, (C) Male cells express significantly higher amounts of immunomodulatory genes in both passage schemes, (E) Male cells express significantly higher amounts of angiogenic genes in both passage schemes. Heatmaps were generated to visualize differences in fold change between the p4–5 and p3–5 schemes. (B) Osteogenic genes varied the most between passage schemes for Donors E and G, (D) Immunomodulatory genes varied between most donors with interleukin-6 and −8 being the most variable across donors. (F) Angiogenic gene expression had little variability between passage schemes. Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint. Fold change is plotted as the mean +/− standard error.
Figure 6: Gene expression analysis at Day 56 of culture. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. A custom Nanostring gene expression panel was used to quantify gene expression over the course of the experiment. (A) Male cells have higher expression of osteogenic genes in both passage schemes, (C) Male cells express significantly higher amounts of immunomodulatory genes in both passage schemes, (E) Male cells express significantly higher amounts of angiogenic genes in both passage schemes. Heatmaps were generated to visualize differences in fold change between the p4–5 and p3–5 schemes. (B) Osteogenic genes varied the most between passage schemes for Donors E and G, (D) Immunomodulatory genes varied between most donors with interleukin-6 and −8 being the most variable across donors. (F) Angiogenic gene expression had little variability between passage schemes. Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint. Fold change is plotted as the mean +/− standard error.CC BY-ND · PubMed Central
Figure 7: Osteogenic, immunomodulatory, and angiogenic protein secretion at Day 56. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. A Luminex assay was used to quantify secreted factors. (A) Female cells secrete more SPARC than male cells and there are no sex differences in the other osteogenic factors (B) Male cells secrete more immunomodulatory factors than female cells. (C) Male cells secrete significantly more ANG than female cells. Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint. Cumulative cytokines secreted is plotted as mean +/− standard error.
Figure 7: Osteogenic, immunomodulatory, and angiogenic protein secretion at Day 56. Eight donors (A, B, E, G – male, and C, D, F, H – female) with 2 passage methods (p4–5 and p3–5) were cultured on mineralized collagen scaffolds for 56-days. A Luminex assay was used to quantify secreted factors. (A) Female cells secrete more SPARC than male cells and there are no sex differences in the other osteogenic factors (B) Male cells secrete more immunomodulatory factors than female cells. (C) Male cells secrete significantly more ANG than female cells. Sex symbol (male: ♂, female: ♀) indicates sex-based significance (p<0.05) at the indicated timepoint. Cumulative cytokines secreted is plotted as mean +/− standard error.CC BY-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 2 references

Research works printed but not linked: 69

  1. 2021, Global, regional, and national burden of bone fractures in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019, The Lancet Healthy Longevity, 2, e580, 10.1016/S2666-7568(21)00172-0 · DOI · Paper page
  2. Samarawickrama, K.G ., A Review on Bone Grafting, Bone Substitutes and Bone Tissue Engineering, in Proceedings of the 2nd International Conference on Medical and Health Informatics. 2018, Association for Computing Machinery: Tsukuba, Japan. p. 244–251. · DOI
  3. Finkemeier, C.G. , Bone-Grafting and Bone-Graft Substitutes. JBJS, 2002. 84(3). · DOI
  4. Baldwin, P. , et al., Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery. Journal of Orthopaedic Trauma, 2019. 33(4). · DOI
  5. 2019, Review of bone graft and bone substitutes with an emphasis on fracture surgeries, Biomaterials Research, 23, 9, 10.1186/s40824-019-0157-y · DOI
  6. 10.3928/01477447-20140825-54 · DOI
  7. 2017, Variant Purification of an Allogeneic Bone Block, Acta Stomatol Croat, 51, 141, 10.15644/asc51/2/7 · DOI
  8. 2023, Case report: Tuberculosis recall on bone graft patient, N Am Spine Soc J, 15, 100241
  9. 2013, Mesenchymal Stem Cells in Bone Regeneration, Adv Wound Care (New Rochelle, 2, 306, 10.1089/wound.2012.0420 · DOI
  10. Stamnitz, S. and A. Klimczak , Mesenchymal Stem Cells, Bioactive Factors, and Scaffolds in Bone Repair: From Research Perspectives to Clinical Practice. Cells, 2021. 10(8). · DOI
  11. 2021, Advancing application of mesenchymal stem cell-based bone tissue regeneration, Bioact Mater, 6, 666
  12. Ryan, H. , et al., Ancestral Background Is Underreported in Regenerative Engineering. Regenerative Engineering and Translational Medicine, 2021. · DOI
  13. Moore, E. , et al., Ancestry of cells must be considered in bioengineering. Nature Reviews Materials, 2021. · DOI
  14. 10.1385/JCD:4:2:147 · DOI
  15. 2017, Sex-Differences in Skeletal Growth and Aging, Current Osteoporosis Reports, 15, 70, 10.1007/s11914-017-0349-0 · DOI
  16. Fitzpatrick, L.A ., Sex differences in skeletal development, in Advances in Molecular and Cell Biology. 2004, Elsevier. p. 229–245. · DOI
  17. Ortona, E. , et al., The Role of Sex Differences in Bone Health and Healing. Biology (Basel), 2023. 12(7). · DOI · Paper page
  18. 2022, Sex-Based Difference in Bone Healing: A Review of Recent Pre-clinical Literature, Curr Rev Musculoskelet Med, 15, 651, 10.1007/s12178-022-09803-1 · DOI
  19. 2009, Sex-specific compromised bone healing in female rats might be associated with a decrease in mesenchymal stem cell quantity, Bone, 45, 1065, 10.1016/j.bone.2009.08.005 · DOI
  20. 2021, Differences in Fracture Healing Between Female and Male C57BL/6J Mice, Front Physiol, 12, 712494, 10.3389/fphys.2021.712494 · DOI
  21. 2021, Let’s Talk About Sex-Biological Sex Is Underreported in Biomaterial Studies, Adv Healthc Mater, 10, e2001034, 10.1002/adhm.202001034 · DOI
  22. 10.1007/s11914-017-0413-9 · DOI
  23. 2021, Influence of comorbidities on functional outcomes in patients with surgically treated fragility hip fractures: a retrospective cohort study, BMC Geriatrics, 21, 283, 10.1186/s12877-021-02227-5 · DOI
  24. 10.3109/17453674.2012.747054 · DOI
  25. 10.1038/nrrheum.2012.1 · DOI
  26. Jennifer, J.B. , et al., Concise Review: Bone Marrow-Derived Mesenchymal Stem Cells Change Phenotype Following In Vitro Culture: Implications for Basic Research and the Clinic. Stem Cells, 2014.
  27. 2013, Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells, BMC Medicine, 11, 146, 10.1186/1741-7015-11-146 · DOI · Paper page
  28. 10.1016/j.mad.2007.12.002 · DOI · Paper page
  29. 2015, Correlation between in vitro expansion-related cell stiffening and differentiation potential of human mesenchymal stem cells, Differentiation, 90, 1, 10.1016/j.diff.2015.08.002 · DOI
  30. 2021, In Vitro Culture Expansion Shifts the Immune Phenotype of Human Adipose-Derived Mesenchymal Stem Cells, Front Immunol, 12, 621744, 10.3389/fimmu.2021.621744 · DOI
  31. 2019, The inclusion of zinc into mineralized collagen scaffolds for craniofacial bone repair applications, Acta biomaterialia, 93, 86, 10.1016/j.actbio.2019.05.031 · DOI
  32. 2019, Shape-fitting collagen-PLA composite promotes osteogenic differentiation of porcine adipose stem cells, Journal of the Mechanical Behavior of Biomedical Materials, 95, 21, 10.1016/j.jmbbm.2019.03.017 · DOI
  33. 2016, Evaluation of multi-scale mineralized collagen-polycaprolactone composites for bone tissue engineering, Journal of the mechanical behavior of biomedical materials, 61, 318, 10.1016/j.jmbbm.2016.03.032 · DOI
  34. 2020, Mineralized collagen scaffolds fabricated with amniotic membrane matrix increase osteogenesis under inflammatory conditions, Regenerative Biomaterials, 7, 247, 10.1093/rb/rbaa005 · DOI
  35. 2021, Glycosaminoglycan content of a mineralized collagen scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation, Materialia, 18, 101149, 10.1016/j.mtla.2021.101149 · DOI
  36. 2020, Anisotropic mineralized collagen scaffolds accelerate osteogenic response in a glycosaminoglycan-dependent fashion, RSC Advances, 10, 15629, 10.1039/D0RA01336F · DOI
  37. 2021, Inclusion of a 3D-printed Hyperelastic Bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold, Acta Biomaterialia, 121, 224, 10.1016/j.actbio.2020.11.028 · DOI
  38. 2022, Amnion and chorion matrix maintain hMSC osteogenic response and enhance immunomodulatory and angiogenic potential in a mineralized collagen scaffold, Front Bioeng Biotechnol, 10, 1034701, 10.3389/fbioe.2022.1034701 · DOI
  39. 2015, Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling, Biomaterials science, 3, 533, 10.1039/C4BM00397G · DOI
  40. 10.1016/j.biomaterials.2015.01.059 · DOI
  41. 2016, Nanoparticulate Mineralized Collagen Scaffolds and BMP-9 Induce a Long-Term Bone Cartilage Construct in Human Mesenchymal Stem Cells, Advanced Healthcare Materials, 5, 1821, 10.1002/adhm.201600187 · DOI
  42. 2017, Nonmineralized and Mineralized Collagen Scaffolds Induce Differential Osteogenic Signaling Pathways in Human Mesenchymal Stem Cells, Advanced Healthcare Materials, 6, 1700641, 10.1002/adhm.201700641 · DOI
  43. 2019, Nanoparticulate mineralized collagen glycosaminoglycan materials directly and indirectly inhibit osteoclastogenesis and osteoclast activation, Journal of tissue engineering and regenerative medicine, 13, 823, 10.1002/term.2834 · DOI
  44. 2022, Osteoprotegerin-eluting nanoparticulate mineralized collagen scaffolds improve skull regeneration, Biomater Adv, 145, 213262
  45. 10.1126/sciadv.aaw4991 · DOI
  46. 2016, Nanoparticulate mineralized collagen scaffolds induce in vivo bone regeneration independent of progenitor cell loading or exogenous growth factor stimulation, Biomaterials, 89, 67, 10.1016/j.biomaterials.2016.02.020 · DOI
  47. 2017, A Mineralized Collagen-Polycaprolactone Composite Promotes Healing of a Porcine Mandibular Defect, Tissue Engineering Part A, 24, 943
  48. 2021, Repair of critical-size porcine craniofacial bone defects using a collagen–polycaprolactone composite biomaterial, Biofabrication, 14, 014102
  49. 2023, Evaluation of bacterial attachment on mineralized collagen scaffolds and addition of manuka honey to increase mesenchymal stem cell osteogenesis, Biomaterials, 294, 122015, 10.1016/j.biomaterials.2023.122015 · DOI
  50. 2023, Inflammatory licensed hMSCs exhibit enhanced immunomodulatory capacity in a biomaterial mediated manner, ACS Biomaterials Science & Engineering, 9, 4916, 10.1021/acsbiomaterials.3c00290 · DOI
  51. 2010, Design of a multiphase osteochondral scaffold. II. Fabrication of a mineralized collagen-glycosaminoglycan scaffold, J Biomed Mater Res A, 92, 1066
  52. 2016, Nanoparticulate mineralized collagen scaffolds induce in vivo bone regeneration independent of progenitor cell loading or exogenous growth factor stimulation, Biomaterials, 89, 67, 10.1016/j.biomaterials.2016.02.020 · DOI
  53. Dewey, M.J. , et al., Glycosaminoglycan content of a mineralized collagen scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation. Materialia (Oxf), 2021. 18. · DOI
  54. 2020, Orbital seeding of mesenchymal stromal cells increases osteogenic differentiation and bone-like tissue formation, Journal of Orthopaedic Research®, 38, 1228, 10.1002/jor.24583 · DOI
  55. 2008, Method to analyze three-dimensional cell distribution and infiltration in degradable scaffolds, Tissue Engineering Part C: Methods, 14, 319, 10.1089/ten.tec.2008.0221 · DOI
  56. 2015, Collagen scaffolds incorporating coincident gradations of instructive structural and biochemical cues for osteotendinous junction engineering, Advanced healthcare materials, 4, 831, 10.1002/adhm.201400809 · DOI
  57. 2017, Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine, Stem Cells Translational Medicine, 6, 2173, 10.1002/sctm.17-0129 · DOI
  58. 2008, Cell passage and composition of culture medium effects proliferation and differentiation of human osteoblast-like cells from facial bone, J Physiol Pharmacol, 59, 47
  59. 2023, Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential, Gene Therapy, 30, 369, 10.1038/s41434-022-00367-w · DOI
  60. 10.1186/s41232-019-0111-3 · DOI
  61. 2020, Alkaline phosphatase: Structure, expression and its function in bone mineralization, Gene, 754, 144855, 10.1016/j.gene.2020.144855 · DOI
  62. 2020, RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling, BioMed Research International, 2020, 1
  63. 2021, Stiffness of Nanoparticulate Mineralized Collagen Scaffolds Triggers Osteogenesis via Mechanotransduction and Canonical Wnt Signaling, Macromolecular Bioscience, 21, 2000370, 10.1002/mabi.202000370 · DOI
  64. 2021, Graham Vesey & Sharon McCracken Immune modulation via adipose derived Mesenchymal Stem cells is driven by donor sex in vitro, Scientific Reports, 11, 12454, 10.1038/s41598-021-91870-4 · DOI
  65. 2019, Immunomodulation by mesenchymal stem cells is sex dependent, Cytotherapy, 21, S84, 10.1016/j.jcyt.2019.03.502 · DOI
  66. 2023, Inflammatory licensed hMSCs exhibit enhanced immunomodulatory capacity in a biomaterial mediated manner, ACS Biomaterials Science & Engineering, 9, 4916, 10.1021/acsbiomaterials.3c00290 · DOI
  67. 2019, Bone health in estrogen-free contraception, Osteoporos Int, 30, 2391, 10.1007/s00198-019-05103-6 · DOI
  68. 10.1210/er.2007-0001 · DOI · Paper page
  69. 10.1073/pnas.83.8.2496 · DOI · Paper page

Cited by

Sorted by citations

  • Mesenchymal stem cell secretome for regenerative medicine: Where do we stand?

    Trigo, C. M., Rodrigues, J. S., Camões, S. P., Solá, S., & Miranda, J. P. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2024.05.004 · Cited by 252

    “…variability [246–248] cannot be ignored since MSC activity and, thus, the properties of MSC-secretome can be affected by donor age and sex [246,248,249], with older donors of BM-MSCs having lower proliferation rates [246,249] and osteogenic [246,248], adipogenic and neurogenic [248] capacities.”

See all 17

Metadata

Authors
Kolliopoulos, V., Tiffany, A., Polanek, M., & Harley, B. A. C.
Affiliations
University of Illinois Urbana-Champaign (US)
Corresponding author
Harley, Brendan A.C.
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2023-11-15
DOI
10.1101/2023.11.12.566781
PMC
PMC10680622
OpenAlex
W4388714160
Cited by
17
References
2
Citations by year
2026: 6 · 2025: 6 · 2024: 5
Type
posted content
Language
en
Open access
Licence
cc-by-nd
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nd)
Funders
  • National Science Foundation (1144245, 1746047, DGE‐1 144 245)
  • National Institutes of Health (1144245)
  • University of Illinois at Urbana-Champaign (DGE-1144245)
  • National Institute of General Medical Sciences (T32GM070421)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR077858)
  • National Institute of Dental and Craniofacial Research (R21DE026582, R01DE030491)
  • Carl R. Woese Institute for Genomic Biology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
Keywords
mesenchymal stem cells, donor variability, osteogenic differentiation, donor sex, passage number, bone marrow-derived stem cells, adipose-derived stem cells, cell proliferation, alkaline phosphatase activity, osteoprotegerin, mineral formation, tissue engineering

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: DONOR VARIABILITY IN HUMAN MESENCHYMAL STEM CELL OSTEOGENIC RESPONSE AS A FUNCTION OF PASSAGE CONDITIONS AND DONOR SEX. https://app.cochat.ai/papers/10.1101/2023.11.12.566781
The paper
Kolliopoulos, V., Tiffany, A., Polanek, M., & Harley, B. A. C. (2023). DONOR VARIABILITY IN HUMAN MESENCHYMAL STEM CELL OSTEOGENIC RESPONSE AS A FUNCTION OF PASSAGE CONDITIONS AND DONOR SEX. bioRxiv (Cold Spring Harbor Laboratory). https://doi.org/10.1101/2023.11.12.566781