Research has shown that the therapeutic effect of mesenchymal stem cells (MSCs) is partially due to its secreted factors as opposed to the implantation of the cells into the treated tissue or tissue replacement. MSC secretome, especially in the form of conditioned medium (MSC-CM) is now being explored as an alternative to MSCs transplantation. Despite the observed benefits of MSC-CM, only a few clinical trials have evaluated it and other secretome components in the treatment of eye diseases. This review provides insight into the potential therapeutic use of MSC-CM in eye conditions, such as corneal diseases, dry eye, glaucoma, retinal diseases and uveitis. We discuss the current evidence, some limitations, and the progress that remains to be achieved before clinical translation becomes possible.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. 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. 8(4), 315–317 (2006).
Medline CASGoogle Scholar
2. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif. 3(4), 393–403 (1970).
CASGoogle Scholar
3. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. Int. J. Mol. Sci. 18(9), 1852 (2017). •• This review article is of considerable interest, as it provided valuable information used and cited in our paper.
MedlineGoogle Scholar
4. De Ugarte DA, Alfonso Z, Zuk PA et al. Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. Immunol. Lett. 89(2–3), 267–270 (2003).
MedlineGoogle Scholar
5. Orciani M, Di Primio R. Skin-derived mesenchymal stem cells: isolation, culture, and characterization. Methods Mol. Biol. Clifton NJ. 989, 275–283 (2013).
Medline CASGoogle Scholar
6. De Bari C, Dell'Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 44(8), 1928–1942 (2001).
MedlineGoogle Scholar
7. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl Acad. Sci. U. S. A. 97(25), 13625–13630 (2000).
Medline CASGoogle Scholar
8. Delorme B, Nivet E, Gaillard J et al. The Human Nose Harbors a Niche of Olfactory Ectomesenchymal Stem Cells Displaying Neurogenic and Osteogenic Properties. Stem Cells Dev. 19(6), 853–866 (2010).
Medline CASGoogle Scholar
9. Patki S, Kadam S, Chandra V, Bhonde R. Human breast milk is a rich source of multipotent mesenchymal stem cells: multipotent breast milk stem cells. Hum. Cell 23(2), 35–40 (2010).
Medline CASGoogle Scholar
10. Zheng B, Cao B, Crisan M et al. Prospective identification of myogenic endothelial cells in human skeletal muscle. Nat. Biotechnol. 25(9), 1025–1034 (2007).
Medline CASGoogle Scholar
11. De Bari C, Dell'Accio F, Luyten FP. Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. Arthritis Rheum. 44(1), 85–95 (2001).
MedlineGoogle Scholar
12. Joe AW, Yeung SN. Concise review: identifying limbal stem cells: classical concepts and new challenges. Stem Cells Transl. Med. 3(3), 318–322 (2014).
Medline CASGoogle Scholar
13. Villaron EM, Almeida J, López-Holgado N et al. Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation. Haematologica 89(12), 1421–1427 (2004).
MedlineGoogle Scholar
14. Ulrich D, Muralitharan R, Gargett CE. Toward the use of endometrial and menstrual blood mesenchymal stem cells for cell-based therapies. Expert Opin. Biol. Ther. 13(10), 1387–1400 (2013).
Medline CASGoogle Scholar
15. Wang H, Hung S, Peng S et al. Mesenchymal Stem Cells in the Wharton's Jelly of the Human Umbilical Cord. Stem Cells 22(7), 1330–1337 (2004).
MedlineGoogle Scholar
16. Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells Dayt. Ohio. 22(4), 625–634 (2004).
MedlineGoogle Scholar
17. Sohni A, Verfaillie CM. Mesenchymal Stem Cells Migration Homing and Tracking. Stem Cells Int. 2013, 1–8 (2013).
Google Scholar
18. Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal Stem Cell Migration and Tissue Repair. Cells. 8(8), 784 (2019).
Medline CASGoogle Scholar
19. Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res. Ther. 7(1), 125 (2016).
MedlineGoogle Scholar
20. Gnecchi M, He H, Noiseux N et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 20(6), 661–669 (2006).
Medline CASGoogle Scholar
21. Gnecchi M, He H, Liang OD et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med. 11(4), 367–368 (2005).
Medline CASGoogle Scholar
22. Teixeira-Pinheiro LC, Toledo MF, Nascimento-dos-Santos G, Mendez-Otero R, Mesentier-Louro LA, Santiago MF. Paracrine signaling of human mesenchymal stem cell modulates retinal microglia population number and phenotype in vitro. Exp. Eye Res. 200, 108212 (2020).
Medline CASGoogle Scholar
23. Pawitan JA. Prospect of Stem Cell Conditioned Medium in Regenerative Medicine. BioMed Res. Int. 2014, 1–14 (2014). •• The article was among the early impactful reviews to discuss the prospect of mesenchymal stem cell-conditioned medium (MSC-CM) in regenerative medicine.
Google Scholar
24. Kourembanas S. Exosomes: Vehicles of Intercellular Signaling, Biomarkers, and Vectors of Cell Therapy. Annu. Rev. Physiol. 77(1), 13–27 (2015).
Medline CASGoogle Scholar
25. Hu C, Zhao L, Zhang L, Bao Q, Li L. Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury. Stem Cell Res. Ther. 11(1), 377 (2020).
Medline CASGoogle Scholar
26. Cho YJ, Song HS, Bhang S et al. Therapeutic effects of human adipose stem cell-conditioned medium on stroke. J. Neurosci. Res. 90(9), 1794–1802 (2012).
Medline CASGoogle Scholar
27. Chuang T-J, Lin K-C, Chio C-C, Wang C-C, Chang C-P, Kuo J-R. Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumatic brain injury rats. J. Trauma Acute Care Surg. 73(5), 1161–1167 (2012).
Medline CASGoogle Scholar
28. Cantinieaux D, Quertainmont R, Blacher S et al. Conditioned Medium from Bone Marrow-Derived Mesenchymal Stem Cells Improves Recovery after Spinal Cord Injury in Rats: An Original Strategy to Avoid Cell Transplantation. PLOS ONE 8(8), e69515 (2013).
Medline CASGoogle Scholar
29. Fernández-Francos S, Eiro N, González-Galiano N, Vizoso FJ. Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives. Int. J. Mol. Sci. 22(15), 7850 (2021).
Medline CASGoogle Scholar
30. Sun DZ, Abelson B, Babbar P, Damaser MS. Harnessing the mesenchymal stem cell secretome for regenerative urology. Nat. Rev. Urol. 16(6), 363–375 (2019).
MedlineGoogle Scholar
31. Alonso-Alonso ML, Srivastava GK, Usategui-Martín R, García-Gutierrez MT, Pastor JC, Fernandez-Bueno I. Mesenchymal Stem Cell Secretome Enhancement by Nicotinamide and Vasoactive Intestinal Peptide: A New Therapeutic Approach for Retinal Degenerative Diseases. Stem Cells Int. 2020, 1–14 (2020).
Google Scholar
32. Kay AG, Long G, Tyler G et al. Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis. Sci. Rep. 7(1), 18019 (2017).
MedlineGoogle Scholar
33. Doorn J, Moll G, Le Blanc K, van Blitterswijk C, de Boer J. Therapeutic applications of mesenchymal stromal cells: paracrine effects and potential improvements. Tissue Eng. Part B Rev. 18(2), 101–115 (2012).
Medline CASGoogle Scholar
34. Salih M, Shaharuddin B, Abdelrazeg S. A Concise Review on Mesenchymal Stem Cells for Tissue Engineering with a Perspective on Ocular Surface Regeneration. Curr. Stem Cell Res. Ther. 15(3), 211–218 (2020).
Medline CASGoogle Scholar
35. Volarevic V, Markovic BS, Gazdic M et al. Ethical and Safety Issues of Stem Cell-Based Therapy. Int. J. Med. Sci. 15(1), 36–45 (2018).
Medline CASGoogle Scholar
36. Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat. Biotechnol. 32(3), 252–260 (2014).
Medline CASGoogle Scholar
37. Wen Y-T, Ho Y-C, Lee Y-C, Ding D-C, Liu P-K, Tsai R-K. The Benefits and Hazards of Intravitreal Mesenchymal Stem Cell (MSC) Based-Therapies in the Experimental Ischemic Optic Neuropathy. Int. J. Mol. Sci. 22(4), 2117 (2021).
Medline CASGoogle Scholar
38. Huang H, Kolibabka M, Eshwaran R et al. Intravitreal injection of mesenchymal stem cells evokes retinal vascular damage in rats. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 33(12), 14668–14679 (2019).
Medline CASGoogle Scholar
39. Rasiah PK, Jha KA, Gentry J et al. A Long-Term Safety and Efficacy Report on Intravitreal Delivery of Adipose Stem Cells and Secretome on Visual Deficits After Traumatic Brain Injury. Transl. Vis. Sci. Technol. 11(10), 1 (2022). • Compares the safety of MSC vs its secretome product. It provides evidence for the safety of MSC-based products.
MedlineGoogle Scholar
40. Saban DR, Masli S. Pathobiology of Immune-Mediated Diseases of the Ocular Surface. In: Pathobiology of Human Disease. Elsevier, 2055–2071 (2014). [cited 2023 Jul 29]. Available from: https://linkinghub.elsevier.com/retrieve/pii/B978012386456704702X
Google Scholar
41. Su W, Wan Q, Huang J et al. Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms. J. Allergy Clin. Immunol. 136(2), 423–432.e8 (2015).
Medline CASGoogle Scholar
42. Fernandes-Cunha GM, Na K-S, Putra I et al. Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier. Stem Cells Transl. Med. 8(5), 478–489 (2019).
Medline CASGoogle Scholar
43. Jiang Z, Liu G, Meng F et al. Paracrine effects of mesenchymal stem cells on the activation of keratocytes. Br. J. Ophthalmol. 101(11), 1583–1590 (2017).
MedlineGoogle Scholar
44. Ma S, Yin J, Hao L et al. Exosomes From Human Umbilical Cord Mesenchymal Stem Cells Treat Corneal Injury via Autophagy Activation. Front. Bioeng. Biotechnol. 10, 879192 (2022).
MedlineGoogle Scholar
45. Mittal R, Patel S, Galor A. Alternative therapies for dry eye disease. Curr. Opin. Ophthalmol. 32(4), 348–361 (2021).
MedlineGoogle Scholar
46. Beyazyıldız E, Pınarlı FA, Beyazyıldız Ö et al. Efficacy of Topical Mesenchymal Stem Cell Therapy in the Treatment of Experimental Dry Eye Syndrome Model. Stem Cells Int. 2014, 1–9 (2014).
Google Scholar
47. Lee Y-C, Sun L-Y, Zhang J-R. Protective effects of low-molecular-weight components of adipose stem cell-derived conditioned medium on dry eye syndrome in mice. Sci. Rep. 11(1), 21874 (2021).
Medline CASGoogle Scholar
48. Dietrich J, Roth M, König S, Geerling G, Mertsch S, Schrader S. Analysis of lacrimal gland derived mesenchymal stem cell secretome and its impact on epithelial cell survival. Stem Cell Res. 38, 101477 (2019).
Medline CASGoogle Scholar
49. Harrell CR, Fellabaum C, Arsenijevic A, Markovic BS, Djonov V, Volarevic V. Therapeutic Potential of Mesenchymal Stem Cells and Their Secretome in the Treatment of Glaucoma. Stem Cells Int. 2019, 1–11 (2019). • Provides evidence for the therapeutic potential of MSC secretome for the treatment of glaucoma.
Google Scholar
50. Roubeix C, Denoyer A, Brignole-Baudouin F, Baudouin C. Thérapie cellulaire par cellules souches mésenchymateuses, un nouvel espoir pour les pathologies oculaires. J. Fr. Ophtalmol. 38(8), 764–775 (2015).
Medline CASGoogle Scholar
51. Johnson TV, DeKorver NW, Levasseur VA et al. Identification of retinal ganglion cell neuroprotection conferred by platelet-derived growth factor through analysis of the mesenchymal stem cell secretome. Brain 137(2), 503–519 (2014).
MedlineGoogle Scholar
52. Yu F, Wang Y, Huang C-Q, Lin S-J, Gao R-X, Wu R-Y. Neuroprotective effect of mesenchymal stem cell-derived extracellular vesicles on optic nerve injury in chronic ocular hypertension. Neural Regen. Res. 18(10), 2301–2306 (2023).
MedlineGoogle Scholar
53. Roth S, Dreixler JC, Mathew B et al. Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats. Invest. Ophthalmol. Vis. Sci. 57(7), 3522–3532 (2016).
Medline CASGoogle Scholar
54. Mathew B, Ravindran S, Liu X et al. Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion. Biomaterials 197, 146–160 (2019).
Medline CASGoogle Scholar
55. Usategui-Martín R, Puertas-Neyra K, García-Gutiérrez M-T, Fuentes M, Pastor JC, Fernandez-Bueno I. Human Mesenchymal Stem Cell Secretome Exhibits a Neuroprotective Effect over In Vitro Retinal Photoreceptor Degeneration. Mol. Ther. - Methods Clin. Dev. 17, 1155–1166 (2020).
Medline CASGoogle Scholar
56. Jha KA, Gentry J, Del Mar NA, Reiner A, Sohl N, Gangaraju R. Adipose Tissue-Derived Mesenchymal Stem Cell Concentrated Conditioned Medium Alters the Expression Pattern of Glutamate Regulatory Proteins and Aquaporin-4 in the Retina after Mild Traumatic Brain Injury. J. Neurotrauma 38(12), 1702–1716 (2021).
MedlineGoogle Scholar
57. Mead B, Chamling X, Zack DJ, Ahmed Z, Tomarev S. TNFα-Mediated Priming of Mesenchymal Stem Cells Enhances Their Neuroprotective Effect on Retinal Ganglion Cells. Investig. Opthalmology Vis. Sci. 61(2), 6 (2020).
CASGoogle Scholar
58. Jha KA, Rasiah PK, Gentry J et al. Mesenchymal stem cell secretome protects against oxidative stress-induced ocular blast visual pathologies. Exp. Eye Res. 215, 108930 (2022).
Medline CASGoogle Scholar
59. Kuo S, Chio C, Yeh C et al. Mesenchymal stem cell-conditioned medium attenuates the retinal pathology in amyloid-β-induced rat model of Alzheimer's disease: underlying mechanisms. Aging Cell. 20(5), (2021).
Google Scholar
60. Elshaer SL, Evans W, Pentecost M et al. Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2Akita mouse. Stem Cell Res. Ther. 9(1), 322 (2018).
Medline CASGoogle Scholar
61. Ma M, Li B, Zhang M et al. Therapeutic effects of mesenchymal stem cell-derived exosomes on retinal detachment. Exp. Eye Res. 191, 107899 (2020).
Medline CASGoogle Scholar
62. Bai L, Shao H, Wang H et al. Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis. Sci. Rep. 7(1), 4323 (2017).
MedlineGoogle Scholar
63. Shen Z, Huang W, Liu J, Tian J, Wang S, Rui K. Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases. Front. Immunol. 12, 749192 (2021).
Medline CASGoogle Scholar
64. Shigemoto-Kuroda T, Oh JY, Kim D et al. MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis. Stem Cell Rep. 8(5), 1214–1225 (2017).
Medline CASGoogle Scholar
65. Bermudez MA, Sendon-Lago J, Seoane S et al. Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis. Exp. Eye Res. 149, 84–92 (2016).
Medline CASGoogle Scholar
66. Gu Y, Yao K, Fu Q. Lens regeneration: scientific discoveries and clinical possibilities. Mol. Biol. Rep. 48(5), 4911–4923 (2021).
Medline CASGoogle Scholar
67. Konala VBR, Bhonde R, Pal R. Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. Vitro Cell. Dev. Biol. - Anim. 56(9), 689–700 (2020).
Medline CASGoogle Scholar
68. Nakanishi C, Nagaya N, Ohnishi S et al. Gene and Protein Expression Analysis of Mesenchymal Stem Cells Derived From Rat Adipose Tissue and Bone Marrow. Circ. J. 75(9), 2260–2268 (2011).
Medline CASGoogle Scholar
69. Efimenko A, Dzhoyashvili N, Kalinina N et al. Adipose-Derived Mesenchymal Stromal Cells From Aged Patients With Coronary Artery Disease Keep Mesenchymal Stromal Cell Properties but Exhibit Characteristics of Aging and Have Impaired Angiogenic Potential. Stem Cells Transl. Med. 3(1), 32–41 (2014).
Medline CASGoogle Scholar
70. Sagaradze G, Grigorieva O, Nimiritsky P et al. Conditioned Medium from Human Mesenchymal Stromal Cells: Towards the Clinical Translation. Int. J. Mol. Sci. 20(7), 1656 (2019).
Medline CASGoogle Scholar
71. Baer P, Overath J, Urbschat A et al. Effect of Different Preconditioning Regimens on the Expression Profile of Murine Adipose-Derived Stromal/Stem Cells. Int. J. Mol. Sci. 19(6), 1719 (2018).
MedlineGoogle Scholar
72. Wernly B, Gonçalves I, Kiss A et al. Differences in Stem Cell Processing Lead to Distinct Secretomes Secretion-Implications for Differential Results of Previous Clinical Trials of Stem Cell Therapy for Myocardial Infarction. Biotechnol. J. 12(9), 1600732 (2017).
Google Scholar
73. Pires AO, Mendes-Pinheiro B, Teixeira FG et al. Unveiling the Differences of Secretome of Human Bone Marrow Mesenchymal Stem Cells, Adipose Tissue-Derived Stem Cells, and Human Umbilical Cord Perivascular Cells: A Proteomic Analysis. Stem Cells Dev. 25(14), 1073–1083 (2016).
Medline CASGoogle Scholar
74. Donders R, Bogie JFJ, Ravanidis S et al. Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells. Stem Cells Dev. 27(2), 65–84 (2018).
Medline CASGoogle Scholar
75. Turinetto V, Vitale E, Giachino C. Senescence in Human Mesenchymal Stem Cells: Functional Changes and Implications in Stem Cell-Based Therapy. Int. J. Mol. Sci. 17(7), 1164 (2016).
MedlineGoogle Scholar
76. Zhang Y, Ravikumar M, Ling L, Nurcombe V, Cool SM. Age-Related Changes in the Inflammatory Status of Human Mesenchymal Stem Cells: Implications for Cell Therapy. Stem Cell Rep. 16(4), 694–707 (2021).
Medline CASGoogle Scholar
77. Lange-Consiglio A, Lazzari B, Pizzi F et al. Different Culture Times Affect MicroRNA Cargo in Equine Amniotic Mesenchymal Cells and Their Microvesicles. Tissue Eng. Part C Methods. 24(10), 596–604 (2018).
Medline CASGoogle Scholar
78. Teixeira FG, Panchalingam KM, Anjo SI et al. Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cell secretome? Stem Cell Res. Ther. 6(1), 133 (2015).
MedlineGoogle Scholar
79. Ferreira JR, Teixeira GQ, Santos SG, Barbosa MA, Almeida-Porada G, Gonçalves RM. Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellular Pre-conditioning. Front. Immunol. 9, 2837 (2018). • Discusses the effect of different preconditioning factors on the therapeutic potential of MSC secretome.
Medline CASGoogle Scholar
80. Kang S, Kim S-M, Sung J-H. Cellular and molecular stimulation of adipose-derived stem cells under hypoxia: stimulation of ASCs under hypoxia. Cell Biol. Int. 38(5), 553–562 (2014).
Medline CASGoogle Scholar
81. Bader AM, Klose K, Bieback K et al. Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro. PLOS ONE. 10(9), e0138477 (2015).
MedlineGoogle Scholar
82. Beegle J, Lakatos K, Kalomoiris S et al. Hypoxic Preconditioning of Mesenchymal Stromal Cells Induces Metabolic Changes, Enhances Survival, and Promotes Cell Retention In Vivo. Stem Cells 33(6), 1818–1828 (2015).
Medline CASGoogle Scholar
83. Stubbs SL, Hsiao ST-F, Peshavariya HM, Lim SY, Dusting GJ, Dilley RJ. Hypoxic Preconditioning Enhances Survival of Human Adipose-Derived Stem Cells and Conditions Endothelial Cells In Vitro. Stem Cells Dev. 21(11), 1887–1896 (2012).
Medline CASGoogle Scholar
84. Tsai C-C, Chen Y-J, Yew T-L et al. Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A–p21 by HIF-TWIST. Blood 117(2), 459–469 (2011).
Medline CASGoogle Scholar
85. English K. Mechanisms of mesenchymal stromal cell immunomodulation. Immunol. Cell Biol. 91(1), 19–26 (2013).
Medline CASGoogle Scholar
86. Kim DS, Jang IK, Lee MW et al. Enhanced Immunosuppressive Properties of Human Mesenchymal Stem Cells Primed by Interferon-γ. EBioMedicine. 28, 261–273 (2018).
MedlineGoogle Scholar
87. Maffioli E, Nonnis S, Angioni R et al. Proteomic analysis of the secretome of human bone marrow-derived mesenchymal stem cells primed by pro-inflammatory cytokines. J. Proteomics. 166, 115–126 (2017).
Medline CASGoogle Scholar
88. Lee MJ, Kim J, Kim MY et al. Proteomic Analysis of Tumor Necrosis Factor-α-Induced Secretome of Human Adipose Tissue-Derived Mesenchymal Stem Cells. J. Proteome Res. 9(4), 1754–1762 (2010).
Medline CASGoogle Scholar
89. Onzi GR, Ledur PF, Hainzenreder LD et al. Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. Cytotherapy. 18(7), 828–837 (2016).
Medline CASGoogle Scholar
90. Dehghani L, Khojasteh A, Soleimani M et al. Safety of intraparenchymal injection of allogenic placenta mesenchymal stem cells derived exosome in patients undergoing decompressive craniectomy following malignant middle cerebral artery infarct, a pilot randomized clinical trial. Int. J. Prev. Med. 13(1), 7 (2022).
MedlineGoogle Scholar
91. Maguire G, Friedman P. The safety of a therapeutic product composed of a combination of stem cell released molecules from adipose mesenchymal stem cells and fibroblasts. Future Sci. OA. 6(7), FSO592 (2020). • Evaluates the safety of MSC secretome product. It provides evidence for the safety of MSC-based products.
Medline CASGoogle Scholar

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Received 13 May 2023

Accepted 8 August 2023

Published online 13 September 2023

Published in print October 2023

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Financial & competing interests disclosure

The research was funded by the Ministry of Science and Technology of the People's Republic of China, National Key Research and Development Program of China [2021YFC2301603, 2021YFC2301105] and Natural Science Foundation of Shanxi Province [201901D211339]. 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.

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