Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective
Abstract
:1. Introduction
2. Xenotransplantation Models in HCT Research
3. Mechanism of HSC Homing: From Tail Vein to Bone Marrow
4. The Role of the Bone-Marrow Niche in HSC Homing
5. Measurements of Engraftment in Mouse Models
6. Clonal Hematopoiesis
7. Competitive Repopulation
8. Long-Term Engraftment and Its Influence on Leukemia Relapse
9. Strategies to Improve Engraftment
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Shultz, L.D.; Lyons, L.B.; Burzenski, L.M.; Gott, B.; Chen, X.; Chaleff, S.; Kotb, M.; Gillies, S.D.; King, M.; Mangada, J.; et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J. Immunol. 2005, 174, 6477–6489. [Google Scholar] [CrossRef] [PubMed]
- Ishikawa, F.; Yasukawa, M.; Lyons, B.; Yoshida, S.; Miyamoto, T.; Yoshimoto, G.; Watanabe, T.; Akashi, K.; Shultz, L.D.; Harada, M. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice. Blood 2005, 106, 1565–1573. [Google Scholar] [CrossRef] [PubMed]
- Pearson, T.; Shultz, L.D.; Miller, D.; King, M.; Laning, J.; Fodor, W.; Cuthbert, A.; Burzenski, L.; Gott, B.; Lyons, B.; et al. Non-obese diabetic-recombination activating gene-1 (NOD-Rag1null) interleukin (IL)-2 receptor common gamma chain (IL2r γ null) null mice: A radioresistant model for human lymphohaematopoietic engraftment. Clin. Exp. Immunol. 2008, 154, 270–284. [Google Scholar] [CrossRef]
- Hamilton, N.; Sabroe, I.; Renshaw, S.A. A method for transplantation of human HSCs into zebrafish, to replace humanised murine transplantation models. F1000Research 2018, 7, 594. [Google Scholar] [CrossRef] [PubMed]
- Konantz, M.; Müller, J.S.; Lengerke, C. Zebrafish Xenografts for the In Vivo Analysis of Healthy and Malignant Human Hematopoietic Cells. Methods Mol. Biol. 2019, 2017, 205–217. [Google Scholar] [PubMed]
- Hopper, S.E.; Cuomo, F.; Ferruzzi, J.; Burris, N.S.; Roccabianca, S.; Humphrey, J.D.; Figueroa, C.A. Comparative Study of Human and Murine Aortic Biomechanics and Hemodynamics in Vascular Aging. Front. Physiol. 2021, 12, 746796. [Google Scholar] [CrossRef] [PubMed]
- Bjornson-Hooper, Z.B.; Fragiadakis, G.K.; Spitzer, M.H.; Chen, H.; Madhireddy, D.; Hu, K.; Lundsten, K.; McIlwain, D.R.; Nolan, G.P. A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates. Front. Immunol. 2022, 13, 867015. [Google Scholar] [CrossRef]
- Haas, S.; Trumpp, A.; Milsom, M.D. Causes and Consequences of Hematopoietic Stem Cell Heterogeneity. Cell Stem Cell 2018, 22, 627–638. [Google Scholar] [CrossRef]
- Life Expectancy at Birth (Years). Available online: https://www.who.int/data/gho/data/indicators/indicator-details/GHO/life-expectancy-at-birth-(years) (accessed on 15 December 2023).
- Calvi, L.M.; Link, D.C. The hematopoietic stem cell niche in homeostasis and disease. Blood 2015, 126, 2443–2451. [Google Scholar] [CrossRef]
- Ratajczak, M.Z.; Suszynska, M. Emerging Strategies to Enhance Homing and Engraftment of Hematopoietic Stem Cells. Stem Cell Rev. Rep. 2015, 12, 121–128. [Google Scholar] [CrossRef]
- Zhao, M.; Li, L. Dissecting the bone marrow HSC niches. Cell Res. 2016, 26, 975–976. [Google Scholar] [CrossRef]
- Bigas, A.; Espinosa, L. Hematopoietic stem cells: To be or Notch to be. Blood 2012, 119, 3226–3235. [Google Scholar] [CrossRef]
- Varnum-Finney, B.; Halasz, L.M.; Sun, M.; Gridley, T.; Radtke, F.; Bernstein, I.D. Notch2 governs the rate of generation of mouse long- and short-term repopulating stem cells. J. Clin. Investig. 2011, 121, 1207–1216. [Google Scholar] [CrossRef]
- Maillard, I.; Koch, U.; Dumortier, A.; Shestova, O.; Xu, L.; Sai, H.; Pross, S.E.; Aster, J.C.; Bhandoola, A.; Radtke, F.; et al. Canonical Notch Signaling Is Dispensable for the Maintenance of Adult Hematopoietic Stem Cells. Cell Stem Cell 2008, 2, 356–366. [Google Scholar] [CrossRef]
- Xiao, Y.; McGuinness, C.; Doherty-Boyd, W.S.; Salmeron-Sanchez, M.; Donnelly, H.; Dalby, M.J. Current insights into the bone marrow niche: From biology in vivo to bioengineering ex vivo. Biomaterials 2022, 286, 121568. [Google Scholar] [CrossRef]
- Boulais, P.E.; Frenette, P.S. Making sense of hematopoietic stem cell niches. Blood 2015, 125, 2621–2629. [Google Scholar] [CrossRef]
- Calvi, L.M.; Adams, G.B.; Weibrecht, K.W.; Weber, J.M.; Olson, D.P.; Knight, M.C.; Martin, R.P.; Schipani, E.; Divieti, P.; Bringhurst, F.R.; et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 2003, 425, 841–846. [Google Scholar] [CrossRef]
- Hosokawa, K.; Arai, F.; Yoshihara, H.; Iwasaki, H.; Hembree, M.; Yin, T.; Nakamura, Y.; Gomei, Y.; Takubo, K.; Shiama, H.; et al. Cadherin-Based Adhesion Is a Potential Target for Niche Manipulation to Protect Hematopoietic Stem Cells in Adult Bone Marrow. Cell Stem Cell 2010, 6, 194–198. [Google Scholar] [CrossRef]
- Zhang, J.; Niu, C.; Ye, L.; Huang, H.; He, X.; Tong, W.-G.; Ross, J.; Haug, J.; Johnson, T.; Feng, J.Q.; et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003, 425, 836–841. [Google Scholar] [CrossRef]
- Frenette, P.S.; Subbarao, S.; Mazo, I.B.; von Andrian, U.H.; Wagner, D.D. Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow. Proc. Natl. Acad. Sci. USA 1998, 95, 14423–14428. [Google Scholar] [CrossRef]
- Mazo, I.B.; Gutierrez-Ramos, J.-C.; Frenette, P.S.; Hynes, R.O.; Wagner, D.D.; von Andrian, U.H. Hematopoietic Progenitor Cell Rolling in Bone Marrow Microvessels: Parallel Contributions by Endothelial Selectins and Vascular Cell Adhesion Molecule 1. J. Exp. Med. 1998, 188, 465–474. [Google Scholar] [CrossRef]
- Ibbotson, G.C.; Doig, C.; Kaur, J.; Gill, V.; Ostrovsky, L.; Fairhead, T.; Kubes, P. Functional α4-integrin: A newly identified pathway of neutrophil recruitment in critically ill septic patients. Nat. Med. 2001, 7, 465–470. [Google Scholar] [CrossRef]
- Peled, A.; Kollet, O.; Ponomaryov, T.; Petit, I.; Franitza, S.; Grabovsky, V.; Slav, M.M.; Nagler, A.; Lider, O.; Alon, R.; et al. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34+ cells: Role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 2000, 95, 3289–3296. [Google Scholar] [CrossRef]
- Lapidot, T.; Dar, A.; Kollet, O. How do stem cells find their way home? Blood 2005, 106, 1901–1910. [Google Scholar] [CrossRef]
- Plett, P.; Frankovitz, S.M.; Wolber, F.M.; Abonour, R.; Orschell-Traycoff, C.M. Treatment of circulating CD34+ cells with SDF-1α or anti-CXCR4 antibody enhances migration and NOD/SCID repopulating potential. Exp. Hematol. 2002, 30, 1061–1069. [Google Scholar] [CrossRef]
- Sugiyama, T.; Kohara, H.; Noda, M.; Nagasawa, T. Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Chemokine Signaling in Bone Marrow Stromal Cell Niches. Immunity 2006, 25, 977–988. [Google Scholar] [CrossRef]
- Marchese, A.; Raiborg, C.; Santini, F.; Keen, J.H.; Stenmark, H.; Benovic, J.L. The E3 Ubiquitin Ligase AIP4 Mediates Ubiquitination and Sorting of the G Protein-Coupled Receptor CXCR4. Dev. Cell 2003, 5, 709–722. [Google Scholar] [CrossRef]
- Rossi, L.; Manfredini, R.; Bertolini, F.; Ferrari, D.; Fogli, M.; Zini, R.; Salati, S.; Salvestrini, V.; Gulinelli, S.; Adinolfi, E.; et al. The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration. Blood 2006, 109, 533–542. [Google Scholar] [CrossRef]
- Adamiak, M.; Borkowska, S.; Wysoczynski, M.; Suszynska, M.; Kucia, M.; Rokosh, G.; Abdel-Latif, A.; Ratajczak, J.; Ratajczak, M.Z. Evidence for the involvement of sphingosine-1-phosphate in the homing and engraftment of hematopoietic stem cells to bone marrow. Oncotarget 2015, 6, 18819–18828. [Google Scholar] [CrossRef]
- Di Virgilio, F.; Chiozzi, P.; Ferrari, D.; Falzoni, S.; Sanz, J.M.; Morelli, A.; Torboli, M.; Bolognesi, G.; Baricordi, O.R. Nucleotide receptors: An emerging family of regulatory molecules in blood cells. Blood 2001, 97, 587–600. [Google Scholar] [CrossRef]
- Liles, W.C.; Broxmeyer, H.E.; Rodger, E.; Wood, B.; Hübel, K.; Cooper, S.; Hangoc, G.; Bridger, G.J.; Henson, G.W.; Calandra, G.; et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 2003, 102, 2728–2730. [Google Scholar] [CrossRef]
- Onai, N.; Zhang, Y.Y.; Yoneyama, H.; Kitamura, T.; Ishikawa, S.; Matsushima, K. Impairment of lymphopoiesis and myelopoiesis in mice reconstituted with bone marrow–hematopoietic progenitor cells expressing SDF-1–intrakine. Blood 2000, 96, 2074–2080. [Google Scholar] [CrossRef]
- Notta, F.; Doulatov, S.; Laurenti, E.; Poeppl, A.; Jurisica, I.; Dick, J.E. Isolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment. Science 2011, 333, 218–221. [Google Scholar] [CrossRef]
- Al-Amoodi, A.S.; Li, Y.; Al-Ghuneim, A.; Allehaibi, H.; Isaioglou, I.; Esau, L.E.; AbuSamra, D.B.; Merzaban, J.S. Refining the migration and engraftment of short-term and long-term HSCs by enhancing homing-specific adhesion mechanisms. Blood Adv. 2022, 6, 4373–4391. [Google Scholar] [CrossRef]
- Kunisaki, Y.; Bruns, I.; Scheiermann, C.; Ahmed, J.; Pinho, S.; Zhang, D.; Mizoguchi, T.; Wei, Q.; Lucas, D.; Ito, K.; et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature 2013, 502, 637–643. [Google Scholar] [CrossRef]
- Chen, J.; Hendriks, M.; Chatzis, A.; Ramasamy, S.K.; Kusumbe, A.P. Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease. J. Bone Miner. Res. 2020, 35, 2103–2120. [Google Scholar] [CrossRef]
- Bryder, D.; Rossi, D.J.; Weissman, I.L. Hematopoietic stem cells: The paradigmatic tissue-specific stem cell. Am. J. Pathol. 2006, 169, 439–443. [Google Scholar] [CrossRef]
- Mazurier, F.; Doedens, M.; Gan, O.I.; Dick, J.E. Rapid myeloerythroid repopulation after intrafemoral transplantation of NOD-SCID mice reveals a new class of human stem cells. Nat. Med. 2003, 9, 959–963. [Google Scholar] [CrossRef]
- Uchida, N.; Dykstra, B.; Lyons, K.J.; Leung, F.Y.; Eaves, C.J. Different in vivo repopulating activities of purified hematopoietic stem cells before and after being stimulated to divide in vitro with the same kinetics. Exp. Hematol. 2003, 31, 1338–1347. [Google Scholar] [CrossRef]
- Dykstra, B.; Ramunas, J.; Kent, D.; McCaffrey, L.; Szumsky, E.; Kelly, L.; Farn, K.; Blaylock, A.; Eaves, C.; Jervis, E. High-resolution video monitoring of hematopoietic stem cells cultured in single-cell arrays identifies new features of self-renewal. Proc. Natl. Acad. Sci. USA 2006, 103, 8185–8190. [Google Scholar] [CrossRef]
- Jaiswal, S.; Ebert, B.L. Clonal hematopoiesis in human aging and disease. Science 2019, 366, 586. [Google Scholar] [CrossRef]
- Genovese, G.; Kähler, A.K.; Handsaker, R.E.; Lindberg, J.; Rose, S.A.; Bakhoum, S.F.; Chambert, K.; Mick, E.; Neale, B.M.; Fromer, M.; et al. Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence. N. Engl. J. Med. 2014, 371, 2477–2487. [Google Scholar] [CrossRef]
- Skead, K.; Houle, A.A.; Abelson, S.; Agbessi, M.; Bruat, V.; Lin, B.; Soave, D.; Shlush, L.; Wright, S.; Dick, J.; et al. Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood. Nat. Commun. 2021, 12, 4921. [Google Scholar] [CrossRef]
- Silver, A.J.; Jaiswal, S. Clonal hematopoiesis: Pre-cancer PLUS. Adv. Cancer Res. 2019, 141, 85–128. [Google Scholar]
- Busque, L.; Patel, J.P.; Figueroa, M.E.; Vasanthakumar, A.; Provost, S.; Hamilou, Z.; Mollica, L.; Li, J.; Viale, A.; Heguy, A.; et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat. Genet. 2012, 44, 1179–1181. [Google Scholar] [CrossRef]
- Steensma, D.P.; Bejar, R.; Jaiswal, S.; Lindsley, R.C.; Sekeres, M.A.; Hasserjian, R.P.; Ebert, B.L. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 2015, 126, 9–16. [Google Scholar] [CrossRef]
- Xie, M.; Lu, C.; Wang, J.; McLellan, M.D.; Johnson, K.J.; Wendl, M.C.; McMichael, J.F.; Schmidt, H.K.; Yellapantula, V.; Miller, C.A.; et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat. Med. 2014, 20, 1472–1478. [Google Scholar] [CrossRef]
- Cho, R.H.; Sieburg, H.B.; Muller-Sieburg, C.E. A new mechanism for the aging of hematopoietic stem cells: Aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 2008, 111, 5553–5561. [Google Scholar] [CrossRef]
- Dykstra, B.; Kent, D.; Bowie, M.; McCaffrey, L.; Hamilton, M.; Lyons, K.; Lee, S.-J.; Brinkman, R.; Eaves, C. Long-Term Propagation of Distinct Hematopoietic Differentiation Programs In Vivo. Cell Stem Cell 2007, 1, 218–229. [Google Scholar] [CrossRef]
- Biasco, L.; Pellin, D.; Scala, S.; Dionisio, F.; Basso-Ricci, L.; Leonardelli, L.; Scaramuzza, S.; Baricordi, C.; Ferrua, F.; Cicalese, M.P.; et al. In Vivo Tracking of Human Hematopoiesis Reveals Patterns of Clonal Dynamics during Early and Steady-State Reconstitution Phases. Cell Stem Cell 2016, 19, 107–119. [Google Scholar] [CrossRef]
- Tothova, Z.; Krill-Burger, J.M.; Popova, K.D.; Landers, C.C.; Sievers, Q.L.; Yudovich, D.; Belizaire, R.; Aster, J.C.; Morgan, E.A.; Tsherniak, A.; et al. Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia. Cell Stem Cell 2017, 21, 547–555.e8. [Google Scholar] [CrossRef] [PubMed]
- Jaiswal, S.; Natarajan, P.; Silver, A.J.; Gibson, C.J.; Bick, A.G.; Shvartz, E.; McConkey, M.; Gupta, N.; Gabriel, S.; Ardissino, D.; et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N. Engl. J. Med. 2017, 377, 111–121. [Google Scholar] [CrossRef]
- Yuan, N.; Wei, W.; Ji, L.; Qian, J.; Jin, Z.; Liu, H.; Xu, L.; Li, L.; Zhao, C.; Gao, X.; et al. Young donor hematopoietic stem cells revitalize aged or damaged bone marrow niche by transdifferentiating into functional niche cells. Aging Cell 2023, 22, e13889. [Google Scholar] [CrossRef] [PubMed]
- Stewart, F.; Crittenden, R.; Lowry, P.; Pearson-White, S.; Quesenberry, P.J. Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice. Blood 1993, 81, 2566–2571. [Google Scholar] [CrossRef] [PubMed]
- Brecher, G.; Ansell, J.D.; Micklem, H.S.; Tjio, J.H.; Cronkite, E.P. Special proliferative sites are not needed for seeding and proliferation of transfused bone marrow cells in normal syngeneic mice. Proc. Natl. Acad. Sci. USA 1982, 79, 5085–5087. [Google Scholar] [CrossRef]
- Saxe, D.F.; Boggs, S.S.; Boggs, D.R. Transplantation of chromosomally marked syngeneic marrow cells into mice not subjected to hematopoietic stem cell depletion. Exp. Hematol. 1984, 12, 277–283. [Google Scholar] [PubMed]
- Shimoto, M.; Sugiyama, T.; Nagasawa, T. Numerous niches for hematopoietic stem cells remain empty during homeostasis. Blood 2017, 129, 2124–2131. [Google Scholar] [CrossRef]
- Ding, L.; Saunders, T.L.; Enikolopov, G.; Morrison, S.J. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 2012, 481, 457–462. [Google Scholar] [CrossRef]
- Zhang, B.; Ho, Y.W.; Huang, Q.; Maeda, T.; Lin, A.; Lee, S.-U.; Hair, A.; Holyoake, T.L.; Huettner, C.; Bhatia, R. Altered Microenvironmental Regulation of Leukemic and Normal Stem Cells in Chronic Myelogenous Leukemia. Cancer Cell 2012, 21, 577–592. [Google Scholar] [CrossRef]
- Schepers, K.; Pietras, E.M.; Reynaud, D.; Flach, J.; Binnewies, M.; Garg, T.; Wagers, A.J.; Hsiao, E.C.; Passegué, E. Myeloproliferative Neoplasia Remodels the Endosteal Bone Marrow Niche into a Self-Reinforcing Leukemic Niche. Cell Stem Cell 2013, 13, 285–299. [Google Scholar] [CrossRef]
- Li, T.; Luo, C.; Zhang, J.; Wei, L.; Sun, W.; Xie, Q.; Liu, Y.; Zhao, Y.; Xu, S.; Wang, L. Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis. Stem Cell Res. Ther. 2021, 12, 246. [Google Scholar] [CrossRef] [PubMed]
- Arora, M.; Burns, L.J.; Barker, J.N.; Miller, J.S.; Defor, T.E.; Olujohungbe, A.B.; Weisdorf, D.J. Randomized comparison of granulocyte colony-stimulating factor versus granulocyte-macrophage colony-stimulating factor plus intensive chemotherapy for peripheral blood stem cell mobilization and autologous transplantation in multiple myeloma. Biol. Blood Marrow Transplant. 2004, 10, 395–404. [Google Scholar] [CrossRef] [PubMed]
- Hu, L.; Cheng, H.; Gao, Y.; Shi, M.; Liu, Y.; Hu, Z.; Xu, J.; Qiu, L.; Yuan, W.; Leung, A.Y.-H.; et al. Antioxidant N-acetyl-l-cysteine increases engraftment of human hematopoietic stem cells in immune-deficient mice. Blood 2014, 124, e45–e48. [Google Scholar] [CrossRef] [PubMed]
- Maude, S.L.; Frey, N.; Shaw, P.A.; Aplenc, R.; Barrett, D.M.; Bunin, N.J.; Chew, A.; Gonzalez, V.E.; Zheng, Z.; Lacey, S.F.; et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 2014, 371, 1507–1517. [Google Scholar] [CrossRef] [PubMed]
- Hu, Y.; Zhou, Y.; Zhang, M.; Ge, W.; Li, Y.; Yang, L.; Wei, G.; Han, L.; Wang, H.; Yu, S.; et al. CRISPR/Cas9-Engineered Universal CD19/CD22 Dual-Targeted CAR-T Cell Therapy for Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia. Clin. Cancer Res. 2021, 27, 2764–2772. [Google Scholar] [CrossRef] [PubMed]
- Ravandi, F.; Walter, R.B.; Subklewe, M.; Buecklein, V.; Jongen-Lavrencic, M.; Paschka, P.; Ossenkoppele, G.J.; Kantarjian, H.M.; Hindoyan, A.; Agarwal, S.K.; et al. Updated results from phase I dose-escalation study of AMG 330, a bispecific T-cell engager molecule, in patients with relapsed/refractory acute myeloid leukemia (R/R AML). J. Clin. Oncol. 2020, 38, 7508. [Google Scholar] [CrossRef]
- Sheng, Y.; Yu, C.; Liu, Y.; Hu, C.; Ma, R.; Lu, X.; Ji, P.; Chen, J.; Mizukawa, B.; Huang, Y.; et al. FOXM1 regulates leukemia stem cell quiescence and survival in MLL-rearranged AML. Nat. Commun. 2020, 11, 928. [Google Scholar] [CrossRef]
- Zhao, C.; Chen, A.; Jamieson, C.H.; Fereshteh, M.; Abrahamsson, A.; Blum, J.; Kwon, H.Y.; Kim, J.; Chute, J.P.; Rizzieri, D.; et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 2009, 458, 776–779. [Google Scholar] [CrossRef]
- Agarwal, P.; Isringhausen, S.; Li, H.; Paterson, A.J.; He, J.; Gomariz, Á.; Nagasawa, T.; Nombela-Arrieta, C.; Bhatia, R. Mesenchymal Niche-Specific Expression of Cxcl12 Controls Quiescence of Treatment-Resistant Leukemia Stem Cells. Cell Stem Cell 2019, 24, 769–784.e6. [Google Scholar] [CrossRef]
- Borthakur, G.; Zeng, Z.; Cortes, J.E.; Chen, H.C.; Huang, X.; Konopleva, M.; Ravandi, F.; Kadia, T.; Patel, K.P.; Daver, N.; et al. Phase 1 study of combinatorial sorafenib, G-CSF, and plerixafor treatment in relapsed/refractory, FLT3-ITD-mutated acute myelogenous leukemia patients. Am. J. Hematol. 2020, 95, 1296–1303. [Google Scholar] [CrossRef]
- Mori, T.; Kikuchi, T.; Yamazaki, R.; Koda, Y.; Saburi, M.; Sakurai, M.; Shigematsu, N.; Okamoto, S.; Kato, J. Phase 1 study of plerixafor in combination with total body irradiation-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation. Int. J. Hematol. 2021, 113, 877–883. [Google Scholar] [CrossRef] [PubMed]
- Du, J.; Yu, D.; Han, X.; Zhu, L.; Huang, Z. Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis. JAMA Netw. Open 2021, 4, e219807. [Google Scholar] [CrossRef] [PubMed]
- Pidala, J.; Kim, J.; Schell, M.; Lee, S.J.; Hillgruber, R.; Nye, V.; Ayala, E.; Alsina, M.; Betts, B.; Bookout, R.; et al. Race/ethnicity affects the probability of finding an HLA-A, -B, -C and -DRB1 allele-matched unrelated donor and likelihood of subsequent transplant utilization. Bone Marrow Transplant. 2012, 48, 346–350. [Google Scholar] [CrossRef] [PubMed]
- Alotaibi, H.; Aljurf, M.; de Latour, R.; Alfayez, M.; Bacigalupo, A.; El Fakih, R.; Schrezenmeier, H.; Ahmed, S.O.; Gluckman, E.; Iqbal, S.; et al. Upfront Alternative Donor Transplant versus Immunosuppressive Therapy in Patients with Severe Aplastic Anemia Who Lack a Fully HLA-Matched Related Donor: Systematic Review and Meta-Analysis of Retrospective Studies, on Behalf of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation. Transplant. Cell. Ther. 2021, 28, 105.e1–105.e7. [Google Scholar] [CrossRef]
- Cashen, A.; Lopez, S.; Gao, F.; Calandra, G.; MacFarland, R.; Badel, K.; DiPersio, J. A Phase II Study of Plerixafor (AMD3100) plus G-CSF for Autologous Hematopoietic Progenitor Cell Mobilization in Patients with Hodgkin Lymphoma. Biol. Blood Marrow Transplant. 2008, 14, 1253–1261. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Goncalves, K.A.; Raskó, T.; Pande, A.; Gil, S.; Liu, Z.; Izsvak, Z.; Papayannopoulou, T.; Davis, J.C., Jr.; Kiem, H.-P.; et al. Single-dose MGTA-145/plerixafor leads to efficient mobilization and in vivo transduction of HSCs with thalassemia correction in mice. Blood Adv. 2021, 5, 1239. [Google Scholar] [CrossRef] [PubMed]
- Manesia, J.K.; Maganti, H.B.; Almoflehi, S.; Jahan, S.; Hasan, T.; Pasha, R.; McGregor, C.; Dumont, N.; Laganière, J.; Audet, J.; et al. AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of hematopoietic stem cells. Cell Rep. Methods 2023, 3, 100663. [Google Scholar] [CrossRef] [PubMed]
- Gao, J.; Li, Y.; Lu, S.; Wang, M.; Yang, Z.; Yan, X.; Zheng, Y. Enhanced in vivo motility of human umbilical cord blood hematopoietic stem/progenitor cells introduced via intra−bone marrow injection into xenotransplanted NOD/SCID mouse. Exp. Hematol. 2009, 37, 990–997. [Google Scholar] [CrossRef]
- Maganti, H.B.; Bailey, A.J.M.; Kirkham, A.M.; Shorr, R.; Pineault, N.; Allan, D.S. Persistence of CRISPR/Cas9 Gene Edited Hematopoietic Stem Cells Following Transplantation: A Systematic Review and Meta-Analysis of Preclinical Studies. STEM CELLS Transl. Med. 2021, 10, 996–1007. [Google Scholar] [CrossRef]
- Janzen, V.; Forkert, R.; Fleming, H.E.; Saito, Y.; Waring, M.T.; Dombkowski, D.M.; Cheng, T.; DePinho, R.A.; Sharpless, N.E.; Scadden, D.T. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 2006, 443, 421–426. [Google Scholar] [CrossRef]
- Maier, B.; Gluba, W.; Bernier, B.; Turner, T.; Mohammad, K.; Guise, T.; Sutherland, A.; Thorner, M.; Scrable, H. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 2004, 18, 306–319. [Google Scholar] [CrossRef] [PubMed]
- Tyner, S.D.; Venkatachalam, S.; Choi, J.; Jones, S.; Ghebranious, N.; Igelmann, H.; Lu, X.; Soron, G.; Cooper, B.; Brayton, C.; et al. p53 mutant mice that display early ageing-associated phenotypes. Nature 2002, 415, 45–53. [Google Scholar] [CrossRef] [PubMed]
- Mantel, C.R.; O’leary, H.A.; Chitteti, B.R.; Huang, X.; Cooper, S.; Hangoc, G.; Brustovetsky, N.; Srour, E.F.; Lee, M.R.; Messina-Graham, S.; et al. Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock. Cell 2015, 161, 1553–1565. [Google Scholar] [CrossRef] [PubMed]
- Capitano, M.L.; Hangoc, G.; Cooper, S.; Broxmeyer, H.E. Mild Heat Treatment Primes Human CD34+ Cord Blood Cells for Migration Toward SDF-1α and Enhances Engraftment in an NSG Mouse Model. Stem Cells 2015, 33, 1975–1984. [Google Scholar] [CrossRef]
Engraftment Factors | Function | Study Model | Influence on Engraftment | References |
---|---|---|---|---|
Stromal-cell-derived factor-1 (SDF-1) also known as CXCL12 | Chemokine isolated from stromal fibroblasts and abundantly expressed in BM. | NOD/LtSz-scid/scid (NOD/SCID) mice and MxCre-CXCR4f/null mice and C57BL/6 | Actuates and promotes HSC maintenance and improves engraftment | Lapidot, T. 2005 [25] Plett, P. et al. 2002 [27] Onai, N. et al. 2000 [33] |
Notch ligands | Signal through Jagged-1 generates short-term progenitor cells and long-term HSCs post-myeloablation, hindering myeloid differentiation | Transgenic Mice: Mx-Cre+ × ROSADNMAML/+ mice; C57BL/6 (B6, CD45.2+); and (B6-SJL, CD45.1+) | Supports HSC self-renewal and improves engraftment | Varnum-Finney, B. et al. 2011 [14] Maillard, I. et al. 2008 [15] |
Lepr and nestin + reticular cells | Associated with the regulation of HSC quiescence and proliferation | Transgenic Mice: Tie2-cre and leptin receptor (LepR)-cre mice and Col1-caPPR mice | Improves HSC frequency in the bone marrow | Xiao, Y. et al. 2022 [16] Boulais, P. E. et al. 2015 [17] |
N-cadherin | Osteoblast direct interactions via N-cadherin-mediated adhesion support HSC function | Transgenic mice: Scl-tTA::TRE-BCR/ABL (BA) double-transgenic mouse—CML | Positively regulates HSCs in BM niche | Hosokawa, K et al. 2010 [19] Schepers, K et al. 2013 [61] |
Osteopontin, angiopoietin-1, and thrombopoietin | Activated osteoblasts can produce osteopontin, angiopoietin-1, and thrombopoietin, which limit HSC expansion and contribute to HSC quiescence | Transgenic mice: Mx1-Cre+Bmpr1afx mutant mice | Shown to positively impact HSC regulation | Hosokawa, K. et al. 2010 [19] |
Intercellular adhesion molecule-1 (ICAM-1) | Plays a role in homing through mediating cellular adhesion interaction | Transgenic mice: C57BL/6 and 129S strains P/E−/− (C57/Bl6J × 129S) Mice lacking the two selectins (P and E−) | Positively regulates HSCs in BM niche | Frenette, P. S. et al. 1998 [21] |
Vascular cell adhesion molecule-1 (VCAM-1) | Plays a role in homing through mediating rolling and firm adhesion of HPC in BM | Transgenic mice: C57/Bl6J × 129S P/E−/− | Positively regulates HSCs in BM niche | Mazo, I. B. et al. 1998 [22] |
α4β1/VLA-4 integrin and lectins | Primary roles in HSC attachment to marrow stromal cells | NOD/SCID | HSC homing by enabling attachment to the vascular endothelium | Peled et al. 2000 [24] |
Adenosine triphosphate (ATP) and uridine triphosphate (UTP) | Extracellular nucleotide (eNTPs) act as potent chemotactic factors in modulating HSC migration in the presence of CXCL12 | NOD/SCID | UTP and ATP (to a lesser extent) modulate HSC motility and homing to BM niche | Rossi, L. et al. 2007 [29] |
Sphingosine-1-phosphate (S1P) | Extracellular nucleotide (eNTPs) act as potent chemotactic factors in modulating HSC migration in the presence of CXCL12 | Transgenic: B6.Cg-Tg(UBC-cre/ERT2)1Ejb/J | Homing of HSPC | Adamiak, M. et al. 2015 [30] |
N-acetyl-L-cysteine (NAC) | Shown to restore the health of BM microenvironment | NOD/SCID and NSG mice | Increase in human HSC engraftment and multilineage hematopoietic differentiation | Hu, L. et al. 2014 [64] |
TGF-B1, TGF-B2, and SLIT2 | TGF-B2 promotes myeloid differentiation and TGF-B1/SLIT2 are HSC retention factors, all support HSC function | BCR/ABL (BA) mice | Regulate quiescence and self-renewal of HSCs | Schepers, K et al. 2013 [61] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Hasan, T.; Pasala, A.R.; Hassan, D.; Hanotaux, J.; Allan, D.S.; Maganti, H.B. Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective. Curr. Oncol. 2024, 31, 603-616. https://doi.org/10.3390/curroncol31020044
Hasan T, Pasala AR, Hassan D, Hanotaux J, Allan DS, Maganti HB. Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective. Current Oncology. 2024; 31(2):603-616. https://doi.org/10.3390/curroncol31020044
Chicago/Turabian StyleHasan, Tanvir, Ajay Ratan Pasala, Dhuha Hassan, Justine Hanotaux, David S. Allan, and Harinad B. Maganti. 2024. "Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective" Current Oncology 31, no. 2: 603-616. https://doi.org/10.3390/curroncol31020044