References

1 - Kazutoshi Takahashi & Shinya Yamanaka , A decade of transcription factor-mediated reprogramming to

pluripotency, Nature Reviews Molecular Cell Biology volume 17, pages 183–193 (2016)

https://www.nature.com/articles/nrm.2016.8

2 - Yuancheng Lu, Benedikt Brommer, Xiao Tian, Anitha Krishnan, Margarita Meer, Chen Wang, ...George M. Church,

Konrad Hochedlinger, Vadim N. Gladyshev, Steve Horvath, ...David A. Sinclair , Reprogramming to recover youthful

epigenetic information and restore vision , Nature volume 588, pages 124–129 (2020)

https://www.nature.com/articles/s41586-020-2975-4

3 - https://med.stanford.edu/news/all-news/2020/03/old-human-cells-rejuvenated-with-stem-cell-technology.html “by

tightly controlling the duration of the exposure to these protein factors ( the Yamanaka factors), we can promote

rejuvenation in multiple human cell types.” By Vittorio Sebastiano, Stanford University.

4 - Suh MR, Lee Y, Kim JY, et al. Human embryonic stem cells express a unique set of microRNAs. Developmental

Biology. 2004 Jun;270(2):488-498

5 - Bi Y, Qiao X, Liu Q, Song S, Zhu K, Qiu X, Zhang X, Jia C, Wang H, Yang Z, Zhang Y, Ji G. Systemic proteomics

and miRNA profile analysis of exosomes derived from human pluripotent stem cells. Stem Cell Res Ther. 2022;13:449.

6 - Matos BM, Stimamiglio MA, Correa A, Robert AW. Human pluripotent stem cell-derived extracellular vesicles: From

now to the future. World J Stem Cells 2023; 15(5): 453-465

7 - Hu G, Xia Y, Zhang J, Chen Y, Yuan J, Niu X, Zhao B, Li Q, Wang Y, Deng Z. ESC-sEVs Rejuvenate Senescent

Hippocampal NSCs by Activating Lysosomes to Improve Cognitive Dysfunction in Vascular Dementia. Adv Sci

(Weinh). 2020;7:1903330.

8 - Li Q, Niu X, Yi Y, Chen Y, Yuan J, Zhang J, Li H, Xia Y, Wang Y, Deng Z. Inducible Pluripotent Stem Cell-Derived

Small Extracellular Vesicles Rejuvenate Senescent Blood-Brain Barrier to Protect against Ischemic Stroke in Aged

Mice. ACS Nano. 2023;17:775-789.

9 - Pan J, Zhao M, Yi X, Tao J, Li S, Jiang Z, Cheng B, Yuan H, Zhang F. Acellular nerve grafts supplemented with

induced pluripotent stem cell-derived exosomes promote peripheral nerve reconstruction and motor function recovery.

Bioact Mater. 2022;15:272-287.

10 - Chen, B., Sun, Y., Zhang, J. et al. Human embryonic stem cell-derived exosomes promote pressure ulcer healing

in aged mice by rejuvenating senescent endothelial cells. Stem Cell Res Ther 10, 142 (2019).

11 - Ding Q, Sun R, Wang P, Zhang H, Xiang M, Meng D, Sun N, Chen AF, Chen S. Protective effects of human

induced pluripotent stem cell-derived exosomes on high glucose-induced injury in human endothelial cells. Exp Ther

Med. 2018;15:4791-4797.

12 - Oh M, Lee J, Kim YJ, Rhee WJ, Park JH. Exosomes Derived from Human Induced Pluripotent Stem Cells

Ameliorate the Aging of Skin Fibroblasts. Int J Mol Sci. 2018;19. https://pubmed.ncbi.nlm.nih.gov/29890746/

13 - Gazdhar, A., Grad, I., Tamò, L. et al. The secretome of induced pluripotent stem cells reduces lung fibrosis in part

by hepatocyte growth factor. Stem Cell Res Ther 5, 123 (2014).

https://stemcellres.biomedcentral.com/articles/10.1186/scrt513

14 - Dayeong Jeong , Wonju Jo, Jaewoong Yoon, Junho Kim, Sachi Gianchandani, Yong Song Gho, Jaesung Park,

Nanovesicles engineered from ES cells for enhanced cell proliferation, Biomaterials actions. 2014 Nov;35(34):9302-

10. https://pubmed.ncbi.nlm.nih.gov/25132601/

15 - Peng Y, Baulier E, Ke Y, Young A, Ahmedli NB, Schwartz SD, Farber DB. Human embryonic stem cells

extracellular vesicles and their effects on immortalized human retinal Muller cells. PLoS One. 2018;13:e0194004.

16 - Wang S, Hou Y, Li X, Song Z, Sun B, Zhang H. Comparison of exosomes derived from induced pluripotent stem

cells and mesenchymal stem cells as therapeutic nanoparticles for treatment of corneal epithelial defects. Aging (Albany

NY). 2020;12:19546-19562.

17 - Hsueh YH, Buddhakosai W, Le PN, Tu YY, Huang HC, Lu HE, Chen WL, Tu YK. Therapeutic effect of induced

pluripotent stem cell -derived extracellular vesicles in an in vitro and in vivo osteoarthritis model. J Orthop

Translat. 2023;38:141-155.

18 - Yu Y, et al. Human embryonic stem-cell-derived exosomes repress NLRP3 inflammasome to alleviate pyroptosis

in nucleus pulposus cells by transmitting miR-302c. Int. J. Mol. Sci. 2023;24:7664–7678. doi: 10.3390/ijms24087664.

19 - Pang Y, et al. Embryonic stem cell-derived exosomes attenuate transverse aortic constriction induced heart failure

by increasing angiogenesis. Front. Cardiovasc. Med. 2021;8:638771. doi: 10.3389/fcvm.2021.638771.

8

20 - Khan M, Nickoloff E, Abramova T, et al. Embryonic stem cell-derived exosomes promote endogenous repair

mechanisms and enhance cardiac function following myocardial infarction. Circ Res. 2015;117(1):52-64.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482130/

21 - Wang Y, Zhang L, Li Y, Chen L, Wang X, Guo W, Zhang X, Qin G, He SH, Zimmerman A, Liu Y, Kim IM, Weintraub

NL, Tang Y. Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective mirnas and prevent

cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol. 2015;192:61–69.

22 - Kishore R, Khan M. More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair. Circ

Res. 2016;118(2):330-343.

23 - Tavakoli Dargani Z, Singla DK. Embryonic stem cell-derived exosomes inhibit doxorubicin-induced TLR4-NLRP3-

mediated cell death-pyroptosis. Am. J. Physiol. Heart Circ. Physiol. 2019;317:H460–H471.

doi: 10.1152/ajpheart.00056.2019.

24 - Singla DK, Johnson TA, Tavakoli Dargani Z. Exosome treatment enhances anti-inflammatory M2 macrophages

and reduces inflammation-induced pyroptosis in doxorubicin-induced cardiomyopathy. Cells. 2019;8:1224–1244.

doi: 10.3390/cells8101224.

25 - Zhou Y, et al. Exosomes derived from induced pluripotent stem cells suppresses M2-type macrophages during

pulmonary fibrosis via miR-302a-3p/TET1 axis. Int. Immunopharmacol. 2021;99:108075.

doi: 10.1016/j.intimp.2021.108075.

26 - Qun Liu, Youkun Bi, Shaole Song, Keqi Zhu, Xinlong Qiao, Huiwen Wang & Guangju Ji, Exosomal miR-17-5p from

human embryonic stem cells prevents pulmonary fibrosis by targeting thrombospondin-2. Stem Cell. Res.

Ther. 2023;14:234.

27 - Povero D, Pinatel EM, Leszczynska A, Goyal NP, Nishio T, Kim J, Kneiber D, de Araujo Horcel L, Eguchi

A, Ordonez PM, Kisseleva T, Feldstein AE. Human induced pluripotent stem cell-derived extracellular vesicles reduce

hepatic stellate cell activation and liver fibrosis. JCI Insight. 2019;5.

28 - Wang N, Li X, Zhong Z, Qiu Y, Liu S, Wu H, Tang X, Chen C, Fu Y, Chen Q, Guo T, Li J, Zhang S, Zern MA, Ma

K, Wang B, Ou Y, Gu W, Cao J, Chen H, Duan Y. 3D hESC exosomes enriched with miR-6766-3p ameliorates liver

fibrosis by attenuating activated stellate cells through targeting the TGFÎ2RII-SMADS pathway. J

Nanobiotechnology. 2021;19:437.

29 - Kwon, M., Song, K., Limanjaya, A. et al. Embryonic stem cell-derived extracellular vesicle-mimetic nanovesicles

rescue erectile function by enhancing penile neurovascular regeneration in the streptozotocin-induced diabetic mouse.

Sci Rep 9, 20072 (2019). https://www.nature.com/articles/s41598-019-54431-4

30 - Kiana Sojoudi, Hossein Azizi & Thomas Skutella A review of the potential of induced pluripotent stem cell-derived

exosome as a novel treatment for male infertility Eng Rev. 2023 Mar 23:1-26.

https://doi.org/10.1080/02648725.2023.2193772

31 - Zhang L, et al. Human pluripotent stem cell-mesenchymal stem cell-derived exosomes promote ovarian granulosa

cell proliferation and attenuate cell apoptosis induced by cyclophosphamide in a POI-like Mouse

Model. Molecules. 2023;28:2112–2129.

32 - Liu M, Qiu Y, Xue Z, Wu R, Li J, Niu X, Yuan J, Wang Y, Wu Q. Small extracellular vesicles derived from embryonic

stem cells restore ovarian function of premature ovarian failure through PI3K/AKT signaling pathway. Stem Cell Res

Ther 2020 Jan 3;11(1):3. doi: 10.1186/s13287-019-1508-2.

32 - Xia Y, Hu G, Chen Y, Yuan J, Zhang J, Wang S, Li Q, Wang Y, Deng Z. Embryonic Stem Cell Derived Small

Extracellular Vesicles Modulate Regulatory T Cells to Protect against Ischemic Stroke. ACS Nano. 2021;15:7370-7385.

33 - Lauren V Schnabel, Christian M Abratte, John C Schimenti, M Julia Bevilaqua Felippe, Jennifer M Cassano, Teresa

L Southard, Jessica A Cross & Lisa A Fortier Induced pluripotent stem cells have similar immunogenic and more potent

immunomodulatory properties compared with bone marrow-derived stromal cells in vitro Regenerative Medicine, 2014,

9, 5 https://doi.org/10.2217/rme.14.29

34 - Kyu Hyun Han, Han Ro, Ju Ho Hong, Eun Mi Lee, Bumrae Cho, Hye Jung Yeom, Myung-Gyu Kim, Kook-Hwan

Oh, Curie Ahn, Jaeseok Yang, Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells

in alloimmune response, Transplant Immunology, Volume 25, Issue 1, 2011.

35 - Collino F, Lopes JA, Tapparo M, Tortelote GG, Kasai-Brunswick TH, Lopes GMC, Almeida DB, Skovronova

R, Wendt CHC, Miranda KR, Bussolati B, Vieyra A, Lindoso RS. Extracellular Vesicles Derived from Induced

Pluripotent Stem Cells Promote Renoprotection in Acute Kidney Injury Model. Cells. 2020;9.

36 - Tarng DC, Tseng WC, Lee PY, Chiou SH, Hsieh SL., Induced Pluripotent stem cell- derived Conditioned medium

attenuates acute kidney injury by down regulating the oxidative stress-related pathway in ischemia-reperfusion rats.

Cell Transplant. 2016;25(3):517-30. doi: 10.3727/096368915X688542.

9

37 - Yu, L., Wen, H., Liu, C., Wang, C., Yu, H., Zhang, K., ... & Liu, N. (2023). Embryonic stem cell-derived extracellular

vesicles rejuvenate senescent cells and antagonize aging in mice. Bioactive Materials, 29, 85-97.

38 - Qianqian Ding, Ruiting Sun, Pingping Wang, Heng Zhang, Meng Xiang, Dan Meng, Ning Sun, Alex F Chen, Sifeng

Chen, Protective effects of human induced pluripotent stem cell-derived exosomes on high glucose-induced injury in

human endothelial cells Exp Ther Med. 2018 Jun;15(6):4791-4797.

39 - Giuffrida D, Rogers IM, Nagy A, Calogero AE, Brown TJ, Casper RF. Human embryonic stem cells secrete soluble

factors that inhibit cancer cell growth. Cell Profil. 2009 Dec;42(6):788-98. doi: 10.1111/j.1365-2184.2009.00640.x.

40 - HeN.,FengG.,LiY.,XuY,XieX.,WangH.,WangY.,OuL.,PeiX.,LiuN.andLiZ. Embryonic stem cell preconditioned

microenvironment suppresses tumorigenic properties in breast cancer. Stem Cell Res Ther. 2016; 7: 95.

41 - Tarasewicz E, Oakes RS, Aviles MO, Straehla J, Chilton KM, Decker JT, Wu J, Shea LD, Jeruss JS. Embryonic

stem cell secreted factors decrease invasiveness of triple-negative breast cancer cells through regulome modulation.

Cancer Biol Ther. 2018, 19: 271-281.

42 - Raof, N.A., Raja, W.K., Castracane, J., Xie, Y. Bioengineering embryonic stem cell microenvironments for exploring

inhibitory effects on metastatic breast cancer cells. Biomaterials 2011, 32, 4130–4139.

43 - Kulesa, P.M.; Kasemeier-Kulesa, J.C.; Teddy, J.M.; Margaryan, N.V.; Seftor, E.A.; Seftor, R.E.; Hendrix, M.J.

Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic

microenvironment. Proc. Natl. Acad. Sci. USA 2006, 103, 3752– 3757.

44 - Kim, M.O.; Kim, S.H.; Oi, N.; Lee, M.H.; Yu, D.H.; Kim, D.J.; Cho, E.J.; Bode, A.M.; Cho, Y.Y.; Bowden, T.G.; et

al. Embryonic stem-cell- preconditioned microenvironment induces loss of cancer cell properties in human melanoma

cells. Pigment Cell Melanoma Res. 2011, 24, 922– 931.

45 - Díez-Torre A, Andrade R, Eguizábal C, López E, Arluzea J, Silió M, Aréchaga J. Reprogramming of melanoma

cells by embryonic microenvironments. Int J Dev Biol. 2009;53(8-10):1563-8.

46 - Postovit LM, Margaryan NV, Seftor EA, Kirschmann DA, Lipavsky A, Wheaton WW, Abbott DE, Seftor REB &

Hendrix MJC. Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive

cancer cells. PNAS. 2008, 105: 4329-4334.

47 - Zhou S, Abdouh M, Arena V, Arena M, Arena Reprogramming Malignant Cancer Cells toward a Benign Phenotype

following Exposure to Human Embryonic Stem Cell Microenvironment. PLoS ONE. 2017, 12: e0169899.

https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0169899

48 - Mary J C Hendrix, Elisabeth A Seftor, Richard E B Seftor, Jennifer Kasemeier-Kulesa, Paul M Kulesa, Lynne-Marie

Postovit, Reprogramming metastatic tumour cells with embryonic microenvironments Nat Rev Cancer actions. 2007

Apr;7(4):246-55. doi: 10.1038/nrc2108. https://pubmed.ncbi.nlm.nih.gov/17384580/

49 - Costa FF, Seftor EA, Bischof JM, Kirschmann DA, Strizzi L, Arndt K, Bonaldo M, Soares MB & Hendrix MJC.

Epigenetically reprogramming metastatic tumor cells with an embryonic microenvironment. Epigenomics 2009, 1: 387–

398.

50 - Kasemeier-Kulesa, J.C.; Teddy, J.M.; Postovit, L.M.; Seftor, E.A.; Seftor, R.E.; Hendrix, M.J.; Kulesa, P.M.

Reprogramming multipotent tumor cells with the embryonic neural crest microenvironment. Dev. Dyn. 2008, 237, 2657–

2666.

51 - Qingwei Zhu, Xiaozheng Ling, Yunlong Yang, Juntao Zhang, Qing Li, Xin Niu, Guowen Hu, Bi Chen, Haiyan

Li, Yang Wang, Zhifeng Deng Embryonic Stem Cells-Derived Exosomes Endowed with Targeting Properties as

Chemotherapeutics Delivery Vehicles for Glioblastoma Therapy, Advanced Science February 2019

https://onlinelibrary.wiley.com/doi/full/10.1002/advs.201801899

52 - Yaddanapudi K., Mitchell RA, Putty K, Willer S, Sharma RK, Yan J, Bodduluri H & Eaton JW. Vaccination with

Embryonic Stem Cells Protects against Lung Cancer: Is a Broad-Spectrum Prophylactic Vaccine against Cancer

Possible? PLoS One. 2012, 7: e42289.

53 - Zhang Z, Chen X, Chang X, Ye X, Li Y, Cui H. Vaccination with embryonic stem cells generates effective antitumor

immunity against ovarian cancer. International Journal of Molecular Medicine. 2012, 147-153.

54 - Li Y, Zeng H, Xu RH, Liu B, Li Z. Vaccination with human pluripotent stem cells generates a broad spectrum of

immunological and clinical responses against colon cancer. Stem Cells. 2009, 27: 3103-11.