Abstract
Currently, regenerative medicine and cellular-based therapy have been in the center of attention worldwide in advanced medical technology. Mesenchymal stem cell (MSC) as a suitable stem cell source for cell-based therapy has been shown to be safe and effective in multiple clinical trial studies (CTSs) of several diseases. Despite the advantages, MSC needs more investigation to enhance its therapeutic application. The CRISPR/Cas system is a novel technique for editing of genes that is being explored as a means to improve MSCs therapeutic usage. In this study, we review the recent studies that explore CRISPR potency in gene engineering of MSCs, which have great relevance in MSC-based therapies. However, CRISPR/Cas technology make possible specific targeting of loci in target genes, but next-generation MSC-based therapies to achieve extensive clinical application need dedicated efforts.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- CRISPR/Cas9:
-
Clustered Regularly Interspaced Short Palindromic Repeats-associated-9
- crRNAs:
-
CRISPR RNAs
- CTSs:
-
Clinical Trial Studies
- DSBs:
-
Double-Strand Breaks
- hESC:
-
human Embryonic Stem Cell
- iPS:
-
Induced Pluripotent Stem Cells
- IVF:
-
in vitro Fertilization
- MSC:
-
Mesenchymal Stem Cell
- PAM:
-
Proto-spacer Adjacent Motif
- SCNT:
-
Somatic-cell Nuclear Transfer
- TALEN:
-
Transcription Activator-like Effector Nucleases
- tracrRNAs:
-
Trans-activating crRNAs
- ZNFs:
-
Zinc-Finger nucleases
References
Albitar A, Rohani B, Will B et al (2018) The application of CRISPR/Cas technology to efficiently model complex Cancer genomes in stem cells. J Cell Biochem 119:134–140. https://doi.org/10.1002/jcb.26195
Ardeshirylajimi A, Soleimani M, Hosseinkhani S et al (2014) A comparative study of osteogenic differentiation human induced pluripotent stem cells and adipose tissue derived mesenchymal stem cells. Cell J 16:235
Ardeshirylajimi A, Vakilian S, Salehi M, Mossahebi-Mohammadi M (2017) Renal differentiation of mesenchymal stem cells seeded on nanofibrous scaffolds improved by human renal tubular cell lines-conditioned medium. ASAIO J 63:356–363. https://doi.org/10.1097/MAT.0000000000000470
Ayala GarcÃa MA, González Yebra B, López Flores AL, Guanà Guerra E (2012) The major histocompatibility complex in transplantation. J Transp Secur 2012:842141–842147. https://doi.org/10.1155/2012/842141
Barrangou R, Fremaux C, Deveau H et al (2007) CRISPR provides acquired resistance against viruses in prokaryotes. Science (80- ) 315:1709–1712. https://doi.org/10.1126/science.1138140
Bayes-Genis A, Roura S, Soler-Botija C et al (2005) Identification of cardiomyogenic lineage markers in untreated human bone marrow–derived Mesenchymal stem cells. Transplant Proc 37:4077–4079. https://doi.org/10.1016/j.transproceed.2005.09.103
Bitinaite J, Wah DA, Aggarwal AK et al (1998) FokI dimerization is required for DNA cleavage. Proc Natl Acad Sci 95:10570–10575. https://doi.org/10.1073/pnas.95.18.10570
Carpenter MK, Rao MS, Carpenter MKRM et al (2015) Concise review: making and using clinically compliant pluripotent stem cell lines. Stem Cells Transl Med 4:381–388. https://doi.org/10.5966/sctm.2014-0202
Carstairs A (2017) Development of in vitro skeletal disease models using CRISPR/Cas9 genome editing in immortalised mesenchymal stem cells
Chamberlain G, Fox J, Ashton B, Middleton J (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25:2739–2749. https://doi.org/10.1634/stemcells.2007-0197
Chen Z, Zhang N, Qi J et al (2017) The structure of the MHC class I molecule of bony fishes provides insights into the conserved nature of the antigen-presenting system. J Immunol 199:3668–3678. https://doi.org/10.4049/jimmunol.1600229
Cong L, Ran FA, Cox D et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science (80-) 339:819–823. https://doi.org/10.1126/science.1231143
Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy Position Statement Cytotherapy 8:315–317. https://doi.org/10.1080/14653240600855905
Filipa A, Almeida D (2017) Genome editing of Mesenchymal stem / stromal cells (MSCs) by CRISPR/Cas9 technology for azurin-based anticancer therapies. Tec LISBOA:1–11
Friedenstein AJ, Chailakhyan RK, Gerasimov UV (1987) Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 20:263–272
Fukami N, Ramachandran S, Saini D et al (2009) Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection. J Immunol 182:309–318
Furuhata Y, Nihongaki Y, Sato M, Yoshimoto K (2017) Control of adipogenic differentiation in mesenchymal stem cells via endogenous gene activation using CRISPR-Cas9. ACS Synth Biol 6:2191–2197. https://doi.org/10.1021/acssynbio.7b00246
Gaj T, Sirk SJ, Shui S, Liu J (2016) Genome-editing technologies: principles and applications. Cold Spring Harb Perspect Biol 8:a023754. https://doi.org/10.1101/cshperspect.a023754
Gerace D, Martiniello-Wilks R, Nassif NT et al (2017) CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success? Stem Cell Res Ther 8:62. https://doi.org/10.1186/s13287-017-0511-8
Golchin A, Farahany TZ (2019) Biological products: cellular therapy and FDA approved products. Stem Cell Rev Rep 15:1–10. https://doi.org/10.1007/s12015-018-9866-1
Golchin A, Farahany TZ, Khojasteh A et al (2018a) The clinical trials of mesenchymal stem cell therapy in skin diseases: an update and concise review. Curr Stem Cell Res Ther 13:22–33. https://doi.org/10.2174/1574888X13666180913123424
Golchin A, Rekabgardan M, Taheri RA, Nourani MR (2018b) Promotion of cell-based therapy: special focus on the cooperation of mesenchymal stem cell therapy and gene therapy for clinical trial studies. In: Turksen K (ed) Advances in experimental medicine and biology. Springer, New York, pp 103–118
Golchin A, Shams F, Kangari P et al (2019) Regenerative medicine: injectable cell-based therapeutics and approved products. Adv Exp Med Biol. Springer, New York, pp 1–21
He X, Tan C, Wang F et al (2016) Knock-in of large reporter genes in human cells via CRISPR/Cas9-induced homology-dependent and independent DNA repair. Nucleic Acids Res 44:e85–e85. https://doi.org/10.1093/nar/gkw064
Hockemeyer D, Wang H, Kiani S et al (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29:731–734. https://doi.org/10.1038/nbt.1927
Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157:1262–1278. https://doi.org/10.1016/j.cell.2014.05.010
Hu X, Li L, Yu X et al (2017) CRISPR/Cas9-mediated reversibly immortalized mouse bone marrow stromal stem cells (BMSCs) retain multipotent features of mesenchymal stem cells (MSCs). Oncotarget 8:111847–111865. https://doi.org/10.18632/oncotarget.22915
Kohlscheen S, Bonig H, Modlich U (2017) Promises and challenges in hematopoietic stem cell gene therapy. Hum Gene Ther 28:782–799. https://doi.org/10.1089/hum.2017.141
Koo T, Lee J, Kim J-S (2015) Measuring and reducing off-target activities of programmable nucleases including CRISPR-Cas9. Mol Cells 38:475–481. https://doi.org/10.14348/molcells.2015.0103
Koonin EV, Makarova KS, Zhang F (2017) Diversity, classification and evolution of CRISPR-Cas systems. Curr Opin Microbiol 37:67–78. https://doi.org/10.1016/j.mib.2017.05.008
Kosaric N, Srifa W, Gurtner GC, Porteus MH (2017) Human Mesenchymal stromal cells engineered to overexpress PDGF-B using CRISPR/Cas9/rAAV6-based tools improve wound healing. Plast Reconstr Surg – Glob Open 5:74. https://doi.org/10.1097/01.GOX.0000516619.11665.84
Li C, Yue S, Busuttil R, Kupiec J, Weglinski BK (2016) Mesenchymal stem cells reprogram macrophage polarization and attenuate liver ischemia and reperfusion injury by regulating notch/Cox2/PGE2 signaling pathway. ATC Abstracts. https://atcmeetingabstracts.com/abstract/mesenchymal-stem-cells-reprogram-macrophage-polarization-and-attenuate-liver-ischemia-and-reperfusion-injury-by-regulating-notchcox2pge2-signaling-pathway/. Accessed 20 Mar 2019
Li X-L, Li G-H, Fu J et al (2018a) Highly efficient genome editing via CRISPR–Cas9 in human pluripotent stem cells is achieved by transient BCL-XL overexpression. Nucleic Acids Res 46:10195–10215. https://doi.org/10.1093/nar/gky804
Li Y, Shao L, Yu Z, Wang J, Wang Y, Yuqing Zhang CH, Zhu B, Zhang L, Pan X, Ouyang W, Liu B, Liang C, Geng Y-j, X yong Y (2018b) Downregulation of B2M in allogeneic MSC by CRISPR technology inhibits immune rejection and enhances cardiac repair | circulation. Circulation 136(Suppl_1). https://www.ahajournals.org/doi/abs/10.1161/circ.136.suppl_1.16195. Accessed 14 Mar 2019
Maeder ML, Gersbach CA (2016) Genome-editing technologies for gene and cell therapy. Mol Ther 24:430–446. https://doi.org/10.1038/mt.2016.10
McElreavey KD, Irvine AI, Ennis KT, McLean WH (1991) Isolation, culture and characterisation of fibroblast-like cells derived from the Wharton’s jelly portion of human umbilical cord. Biochem Soc Trans 19:29S
Meca-Cortés O, Guerra-Rebollo M, Garrido C et al (2017) CRISPR/Cas9-mediated Knockin application in cell therapy: a non-viral procedure for bystander treatment of glioma in mice. Mol Ther – Nucleic Acids 8:395–403. https://doi.org/10.1016/j.omtn.2017.07.012
Nemudryi AA, Valetdinova KR, Medvedev SP, Zakian SM (2014) TALEN and CRISPR/Cas genome editing systems: tools of discovery. Acta Nat 6:19–40
Reiser J, Zhang X-Y, Hemenway CS et al (2005) Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases. Expert Opin Biol Ther 5:1571–1584. https://doi.org/10.1517/14712598.5.12.1571
Samsonraj RM, Rai B, Sathiyanathan P et al (2015) Establishing criteria for human mesenchymal stem cell potency. Stem Cells 33:1878–1891. https://doi.org/10.1002/stem.1982
Sebastiano V, Maeder ML, Angstman JF et al (2011) In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells 29:1717–1726. https://doi.org/10.1002/stem.718
Shen Y, Zhang J, Yu T, Qi C (2018) Generation of PTEN knockout bone marrow mesenchymal stem cell lines by CRISPR/Cas9-mediated genome editing. Cytotechnology 70:783–791. https://doi.org/10.1007/s10616-017-0183-3
Sun S, Xiao J, Huo J et al (2018) Targeting ectodysplasin promotor by CRISPR/dCas9-effector effectively induces the reprogramming of human bone marrow-derived mesenchymal stem cells into sweat gland-like cells. Stem Cell Res Ther 9:8. https://doi.org/10.1186/s13287-017-0758-0
Técnico IS, Ircm CEA, Diderot UP (2015) Knockdown of monocyte chemotactic protein 1 in human mesenchymal stromal cells using two different approaches : shRNA and CRISPR-Cas 9
Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymal stem cells – current trends and future prospective. Biosci Rep. https://doi.org/10.1042/BSR20150025
van den Akker G, van Beuningen H, Blaney Davidson E, van der Kraan P (2016) CRISPR/CAS9 mediated genome engineering of human mesenchymal stem cells. Osteoarthr Cartil 24:S231. https://doi.org/10.1016/j.joca.2016.01.445
Vanoli F, Tomishima M, Feng W et al (2017) CRISPR-Cas9–guided oncogenic chromosomal translocations with conditional fusion protein expression in human mesenchymal cells. Proc Natl Acad Sci 114:3696–3701. https://doi.org/10.1073/pnas.1700622114
Xu X, Gao D, Wang P et al (2018) Efficient homology-directed gene editing by CRISPR/Cas9 in human stem and primary cells using tube electroporation. Sci Rep 8:11649. https://doi.org/10.1038/s41598-018-30227-w
Zhang Z, Zhang Y, Gao F et al (2017) CRISPR/Cas9 genome-editing system in human stem cells: current status and future prospects. Mol Ther – Nucleic Acids 9:230–241. https://doi.org/10.1016/j.omtn.2017.09.009
Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295. https://doi.org/10.1091/mbc.e02-02-0105
Author Contributions
A.G. conceptualized the outline and contents of the article. All authors contributed to writing and editing of the manuscript.
Conflict of Interest
The authors confirm that this article content has no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Golchin, A., Shams, F., Karami, F. (2019). Advancing Mesenchymal Stem Cell Therapy with CRISPR/Cas9 for Clinical Trial Studies. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 8. Advances in Experimental Medicine and Biology(), vol 1247. Springer, Cham. https://doi.org/10.1007/5584_2019_459
Download citation
DOI: https://doi.org/10.1007/5584_2019_459
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-45892-8
Online ISBN: 978-3-030-45893-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)