2024-10-21T12:54:59+08:002020-04-17|
Contact Information
Title
Associate Dean (Research) ,Distinguished Professor
Office
(Office) E12-4015 / (Lab) N22-2003
Phone
(Office) +853 8822 4993 / (Lab) +853 8822 2908
Email
renhexu@um.edu.mo
Consultation Hours

Mon 16:00 – 18:00

Teaching

HSCI4002 Stem Cell Biology and Regenerative Medicine

GEST2001 Biology in Our Daily Life

Research Team
Name Position Office Phone Email
Wenyu XIEResearch Assistant (Lab Representative)N22-2003+853 8822 2908wenyuxie@um.edu.mo
Sen YEResearch AssistantN22-2003+853 8822 2908
Changkun YANGPhD StudentN22-2003+853 8822 2908
Guihui QINPhD StudentN22-2003+853 8822 2908
Peidong HOUPhD StudentN22-2003+853 8822 2908
Weiya HEPhD StudentN22-2003+853 8822 2908
Guoyue WANPhD StudentN22-2003+853 8822 2908
Miaoman YEPhD StudentN22-2003+853 8822 2908
Jinjie WUPhD StudentN22-2003+853 8822 2908
Xianzhuo ZHANGPhD StudentN22-2003+853 8822 2908
Lili YUPhD StudentN22-2003+853 8822 2908
Kailibinuer KadierPhD StudentN22-2003+853 8822 2908
Education
DSc University of Tokyo, Tokyo, Japan
MMed Central South University, Changsha, China
BMed University of South China, Hengyang, China
Positions
2020 – Present Distinguished Professor, Faculty of Health Sciences, University of Macau, Macau
2018 – Present Associate Dean (Research), Faculty of Health Sciences, University of Macau, Macau
2014 – 2020 Professor, Faculty of Health Sciences, University of Macau, Macau
2006 – 2014 Associate Professor, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA
1999 – 2006 Senior Scientist, WiCell Research Institute, Madison, WI, USA
1994 – 1996 Research Fellow, NCI-FCRDC, NIH, Frederick, MD, USA
1992 – 1994 Postdoctoral Fellow, Cancer Aids & Immunology Research Institute, Bar-Ilan University, Ramat Gan, Israel
Research Interests
We are interested in stem cell biology and applications. We first discovered the key factors and signalling to sustain self-renewal and prolonged culture of human embryonic stem cells (hESCs) (Nat. Biotechnol. 2002; Nat. Methods 2005; Cell Stem Cell 2008) and revealed recurrent copy number variations in human induced pluripotent stem cells (iPSCs) (Nat. Biotechnol. 2011). We also mapped the iPSC landscape based on relevant patents and clinical trials global-wide (Nat. Biotechnol. 2024). In 2016, we discovered a new way to derive mesenchymal stem cells (MSCs), which is through differentiation from hESCs via trophoblasts (T-MSC, patented). T-MSCs can chimerize with the mouse blastocyst and contribute to cartilage tissues in the foetus (Cell Rep., 2023). T-MSCs were also used to elucidate how tumor stromal cells assist circulating tumor cells to escape NK cell killing to form metastasis (Adv. Sci. 2024). For therapeutic application, T-MSCs effectively treated mouse and monkey models of multiple sclerosis, colitis (Stem Cell Reports 2014; Stem Cells 2016), osteoarthritis (Theranostics, 2019a), and skin wound (Theranostics, 2019b). T-MSCs also enhance human fat engraftment in nude mice (Biomaterials, 2021). Interestingly, MSC spheroids can be stored under ambient conditions for more than 10 days without need for cryopreservation (Biomaterials 2017). We analysed the distribution, survival, and biosafety of T-MSCs (either dissociated cells or spheroids) in monkeys following i.v. injection (Biomaterials 2022). The U.S. FDA approved T-MSCs as an Investigational New Drug (IND) to treat multiple sclerosis patients. T-MSCs are also studied for their efficacy on patients with diabetic foot ulcer, GvHD, and osteoarthritis in China. We are recruiting PhD students and postdoctoral fellows with training in cellular, molecular, and developmental biology to conduct research along the following directions:

  1. The origin, heterogeneity, and development of MSCs via chimeric embryogenesis;
  2. Fate, immunogenicity, and biosafety of T-MSCs as a therapy;
  3. Role of MSCs in tumorigenesis and tumor microenvironment.
Representative Publications
  1. Fu, S., Huang, B., Li, E., Xu, X., and Xu, R.-H. Chimerization of human ESC-derived extraembryonic cells with the mouse blastocyst. Int’l J. Biol. Sci. In press.
  2. Yi, Y., Qin, G., Yang, H., Jia, H., Zeng, Q., Zheng, D., Ye, S., Zhang, Z., Liu, T.M., Luo, K.Q., Deng, C.-X., and Xu, R.-H. Mesenchymal Stromal Cells Increase the Natural Killer Resistance of Circulating Tumor Cells via Intercellular Signaling of cGAS-STING-IFNβ-HLA. Adv. Sci. 2024.
  3. Lvu L., Feng, Y., Huang, B., Xu, R.-H.*, and Hu, Y.* Mapping global landscape for induced pluripotent stem cells (iPSCs) from patents and clinical trials. Nat. Biotechnol. 2024. *Co-corresponding author.
  4. Huang, B., Fu, S., Hao, Y., Yueng, C.K., Zhang, X., Li, E., Xu, X., Shao, N., and Xu, R.-H. Developmental potency of human ES cell-derived mesenchymal stem cells revealed in mouse embryos following blastocyst injection. Cell Rep. 42(12):113459. doi: 10.1016/j.celrep.2023.113459. 2023.
  5. Yeung, C.K., Yan, Y., Yan, L., Duan, Y., Li, E., Huang, B., Lu, K., Li, K., Zhou, M., Zhang, L., Wu, Y., Luo, K.Q., Ji, W., Xu, R.-H.*, Si, W.* Preclinical safety evaluation and tracing of human mesenchymal stromal cell spheroids following intravenous injection into cynomolgus. Biomaterials 289, 121759, 2022.*Co-corresponding author
  6. Zheng, D., Wang, X., Zhang, Z., Li, E., Yeung, C., Borkar, R., Qin, G., Wu, Y., and Xu, R.-H. Engineering of mesenchymal stem cells resistant to multiple natural killer subtypes. Int’ J. Biol. Sci. 18(1):426-440, 2022.
  7. Borkar R.P., Wang X., Zheng D., Miao Z., Zhang Z., Li E., Wu Y., and Xu R.-H. Human ESC-derived MSCs enhance fat engraftment by promoting adipocyte reaggregation, secreting CCL2 and mobilizing macrophages. Biomaterials 272:120756, 2021.
  8. Wang, X., Jiang, B., Sun, H., Zheng, D., Zhang, Z., Yan, L., Li, E., Wu, Y., and Xu, R.-H. Noninvasive application of mesenchymal stem cell spheres derived from hESC accelerates wound healing in a CXCL12-CXCR4 axis-dependent manner. Theranostics 9(21):6112-28, 2019.
  9. Jiang, B., Fu, X., Yan, L., Li, S., Zhao, D., Wang, X., Duan, Y., Yan, Y., Li, E., Wu, K., Inglis, B.M., Ji, W., Xu, R.-H.*, and Si, W.* Transplantation of human ESC-derived mesenchymal stem cell spheroids ameliorates spontaneous osteoarthritis in rhesus macaques. Theranostics 9(22):6587-600, 2019.*Co-corresponding author
  10. Jiang, B., Yan, L., Wang, X., Li, E., Murphy, K., Vaccaro, K., Li, Y., and Xu, R.-H. Mesenchymal stem cells derived from human pluripotent stem cells, an unlimited and quality-controllable source, for therapeutic applications. Stem Cells  18, 2018.
  11. Jiang, B., Yan, L., Miao, Z., Li, E., Wong, K.H., and Xu, R.-H. Spheroidal formation preserves human stem cells for prolonged time under ambient conditions for facile storage and transportation. Biomaterials133:275-86, 2017.
  12. Zheng, D., Wang, X., and Xu, R.-H. One stone for multiple birds: generating universally compatible human embryonic stem cells. Stem Cells. 34(9):2269-75, Sept. 2016.
  13. Wang, X., Lazorchak, A.S., Song, L., Li, E., Jiang, B., Zhang, Z., and Xu, R.-H. Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage. Stem Cells34(2):380-91, 2016.
  14. Wang, X., Kimbrel, E.A., Ijichi, K. Paul, D., Lazorchak, A.S., Chu, J., Kouris, N.A., Yavanian, G., Lu, S.-J., Pachter, J.S., Crocker, S.J., Lanza, R., and Xu, R.-H.Human ES cell-derived MSC outperform bone marrow MSC in the treatment of an EAE model of multiple sclerosis. Stem Cell Reports 3(1):115-30, 2014.
  15. Luong, M.X., Auerbach, J., Crook, J.M., Daheron, , Hei, D., Lomax, J., Loring, J.F., Ludwig, T., Rooke, H.M., Schlaeger, T.M., Smith, K.P., Stacey, G., Xu, R.-H., and Zeng, F. A call for standardized naming and reporting of human ES and iPS cell lines. Cell Stem Cell 8(4):357-9, 2011.
  16. Martins-Taylor, K., Nisler, B.S., Taapken, S.M., Compton, T., Crandall, L., Montgomery, K.D., Lalande, M., and Xu, R.-H. Recurrent copy number variations in human induced pluripotent stem cells. Nat. Biotechnol. 29(6):488-91, 2011.
  17. Xu, R.-H., Sampsell-Barron, T.L., Gu, F., Root, S., Peck, R.M., Pan, G., Yu, J., Antosiewicz-Bourget, J., Tian, S., Stewart, and Thomson, J.A. NANOG is a direct target of TGF-beta/Activin mediated SMAD signaling in human ES cells.Cell Stem Cell 3(2):196-206, 2008.
  18. Xu, R.-H., Peck, R.M., Li, D.S., Feng, X., Ludwig, T., and Thomson, J.A. Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat. Methods 2(3):185-190, 2005.
  19. Xu, R.-H., Chen, X., Li, D.S., Li, R., Addicks, G.C., Glennon, C., Zwaka, T.P., and Thomson, J.A. BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat. Biotechnol. 20(12):1261-4, 2002.
  20. Xu, R.-H., Dong, Z., Maeno, M., Kim, J., Suzuki, A., Ueno, N., Sredni, B., Colburn, N.H., and Kung, H.-f.: Involvement of Ras/Raf/AP-1 in BMP-4 signaling during Xenopusembryonic development. Proc. Natl. Acad. Sci. U.S.A. 93:834-838, 1996.
Full publications list
Research Grants
2023 – 2026 National Natural Science Foundation (NSFC) General grant #32270842, RMB 540,000
2023 – 2027 Ministry of Science and Technology (MOST) Key R&D grant, RMB 30,000,000
2022 – 2025 Macau Science and Technology Development Fund (FDCT) Key grant #0002-2021-AKP, MOP 8,000,000
2023 – 2024 University of Macau Multi-Year Research Grant (MYRG) #2022-00044-FHS, MOP 336,000
Patents
  1. Xu, R.-H. and Thomson, J.A. Method for generating primate trophoblasts. US patent # US7390657 B2.
  2. Xu, R.-H. and Thomson, J.A. Feeder-independent extended culture of embryonic stem cells. US patent # US7,514,260 B2.
  3. Wang, X. and Xu, R.-H. Trophoblast-derived mesenchymal stem cells (T-MSCs) produced from human embryonic stem cells, methods and uses thereof. US9,725,698, WO2014/011881, EP2872619 A2.
  4. Wang, X., ImStem Biotechnology, Inc., and Xu, R.-H. Mesenchymal-like stem cells derived from human embryonic stem cell, methods and uses thereof. USA #9745551 (29 Aug. 2017), #10226488 (12 Mar. 2019), Japan #2015-521809 (19 Dec. 2017), Australia #2013290146 (20 Dec. 2017), Europe #13816 490.0-1120/2872619 (18 Jan. 2018).
  5. ImStem Biotechnology, Co. Ltd., 王小方，徐仁和：人胚胎幹細胞衍生的間充質樣幹細胞、方法及應用，專利號：CN104487568B。授權日期：15 Aug. 2017。
  6. 徐仁和、蔣斌、燕麗：一种常温条件下保存和运输幹細胞的方法及其所使用的基質。專利號：CN 107306936B。授權日期：2021/01/06。
  7. 徐仁和、楊鵑、鄭德錦、朴政友：角膜上皮細胞和角膜支架及其製備方法和應用。專利號：CN 110468094B。授權日期：2021/04/13。
  8. 徐仁和、王曉燕、蔣斌：一種用於治療皮膚損傷的幹細胞軟膏及其製備方法。專利號：201710366533.5。授權日期：2022/01/05。
  9. Ren-He Xu, Bin Jiang, and Li Yan: Method of differentiating pluripotent stem cells into mesenchymal stem cells under 3D spheroidal culture conditions. US11098281. Date of patent: 24 Aug. 2021.
Awards
2021 粵港澳大灣區高價值專利培育佈局大賽 100強、50強和8強（優秀獎）
2019 Best Teacher Award (Excellence in Research), Faculty of Health Sciences, University of Macau, Macau
2018 Excellent Team Prize, the Grand Final of HKUST One Million Dollar International Entrepreneurship Competition, Guangzhou, China
2018 Finalist, “Fosun Protechting” Global Youth Innovation and Entrepreneurship Competition, Lisbon, Portugal
2018 First place, Bank of China Trophy One Million Dollar Macau Innovation and Entrepreneurship Competition, Macau, China
2009 International Research Award of Royan Institute, Iran
2007 Connecticut United for Research Excellence (CURE): Award of Merit for UConn Stem Cell Core. New Haven, Connecticut, USA
2007 Connecticut State Register and Manual (Annual State Bluebook): Honoree of 2007 awarded by the Secretary of the State Susan Bysiewicz in the State Capitol, Hartford, Connecticut, USA
1997 NIH NCI-FCRDC: Outstanding Science Achievement Award, Frederick, MD, USA
News Coverage
2019. UM Today: “UM achieves breakthrough in developing a non-invasive method to treat skin wounds with stem cell spheres”.
澳門日報
2019. TVB show, “Scoop東張西望”: “UM development – fostering technology and business starters”.
TVB東張西望
2017. UM researchers develop new technology for stem cell storage (澳大幹細胞研究新突破 無需冷藏可保存7天以上)
澳門每日時報
UM Today
Hojemacau
2014. Reuters: ImStem Biotechnology, Inc. makes progress on multiple sclerosis treatment with embryonic stem cells.
http://www.reuters.com/article/2014/06/05/ct-imstem-biotech-idUSnPn5KtTZ2+96+PRN20140605/
2014. UM academic achieves new breakthrough in stem cell research for multiple sclerosis (科研又一突破 澳大學者幹細胞研究有望治療多發性硬化症)
Macau Governmental Portal
UM Today
2013. UConn Today: Health Center Researchers Awarded State Stem Cell Funds. http://today.uconn.edu/blog/2013/06/uconn-health-center-researchers-awarded-state-stem-cell-funds/
2013. UConn Today: New Stem Cell Company Opens Lab at UConn Health Center. http://today.uconn.edu/blog/2013/02/new-stem-cell-company-opens-lab-at-uconn-health-center/
2011. Health Center Today: Researchers Study Genomic Stability of Human Induced Pluripotent Stem Cells.
http://today.uchc.edu/features/2011/jun11/stemcells.html
2010. UConn Today: Four UConn Stem Cell Lines Approved for Use in Federally Funded Research.
http://today.uconn.edu/blog/2010/06/four-uconn-stem-cell-lines-approved-for-use-in-federally-funded-research/
2007. Connecticut United for Research Excellence (CURE): Award of Merit for UConn Stem Cell Core. New Haven, Connecticut on Dec. 4.
2007. Connecticut State Register and Manual (Annual State Bluebook): Honoree of 2007 an annual ceremony hosted by the Secretary of the State Susan Bysiewicz in the State Capitol, Hartford, Connecticut on Oct. 3.
2005. Science: Getting the Mice out of ES Cell Cultures.
http://www.ncbi.nlm.nih.gov/pubmed/?term=15746400
2005. USA Today: Cell Researchers make gains in removing mouse molecules. http://www.usatoday.com/tech/science/genetics/2005-02-18-broken-stems_x.htm
1997. NIH NCI-FCRDC: Outstanding Science Achievement Award, Frederick, MD, U.S.A.
Professional Activities
  • President of Macau Society for Stem Cell Research
  • Member of International Society for Stem Cell Research
  • Member of American Society for Biochemistry and Molecular Biology
  • Member of Chinese Society for Cell Biology
  • Council of Chinese Society for Cell Therapy
  • Council of Chinese Society for Stem Cell ​Research
  • Council of GD-HK-Macau Greater Bay Alliance for Stem Cell Research
  • Council of GD-HK-Macau Greater Bay Alliance for Stem Cell and Precision Medicine Innovation & Industrialization
  • Vice Chair of GD-HK-Macau Greater Bay Alliance for Translational Medicine
Review Services

  • Strategic Trailblazing Program, Chinese Academy of Sciences
  • Thousands Talents (Youth) Program, China
  • Women’s Health Research, Yale University
  • National Natural Science Foundation, China
  • Kansas City Area Life Sciences Institute
  • New York State Stem Cell Science (NYSTEM) Program
  • Maryland State Stem Cell Research Fund
  • Changjiang Scholar Program, China
Editorial Board Member

  • American Journal of Stem Cells
  • Experimental Biology and Medicine
  • Journal of Biological Chemistry (2011-2017)
  • Journal of Cellular Biochemistry
  • International Journal of Biological Sciences (Executive editor)
Current Staff
Angela Enqin LI, Laboratory Manager
Jung Woo PARK, Senior Instructor
Changkun YANG, Research Assistant
Grace Guihui QIN, Research Assistant
Dejin ZHENG, PhD student
Roma BORKAR, PhD student
Borong HUANG, PhD student
Siyi FU, Macau Talent Program PhD student
Haibo PENG, PhD student
Ye YI, PhD student
Sen YE, PhD student
Philip Naderev Panuringan LAGNITON, FYP student
Cleas Junjie HAO, FYP student​