Skip to main content

Table 1 Detailed information and mobilization efficacy of all included novel agents

From: Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies

Agent Detailed information HSPC mobilization efficacy References
1. Cytokines
 SCF Stem cell factor Multi-day SCF alone can induce mobilization; IL-11 plus SCF synergistically enhanced mobilization. Mauch et al. [21]
 IL-11 Interleukin-11 Multi-day IL-11 alone can induce mobilization; IL-11 plus SCF or G-CSF synergistically enhanced mobilization. Mauch et al. [21], Meng et al. [42]
 MIP-1α Macrophage inflammatory protein 1α Single-dose MIP-1α alone induced rapid mobilization; MIP-1α markedly enhanced G-CSF- and AMD3100-induced mobilization. Lord et al. [20], Broxmeyer et al. [52]
 IL-8 Interleukin-8 Single-dose IL-8 alone induced rapid mobilization; the combination of IL-8 with G-CSF or CWHM-823 enhanced mobilization. Wang et al. [24], Zhang et al. [28], de Kruijf et al. [66], Karpova et al. [107]
 MIP-2 Macrophage inflammatory protein-2 Single-dose MIP-2 alone induced rapid mobilization; MIP-2 markedly enhanced G-CSF-induced mobilization. Wang et al. [24]
 FLT-3L Fms-like tyrosine kinase-3 ligand Multi-dose FLT-3L alone can induce mobilization; FLT-3L synergistically enhanced mobilization induced by G-CSF, GM-CSF, IL-8, and AMD 3100. Brasel et al. [22], Sudo et al. [23], Neipp et al. [25], Robinson et al. [33], Robinson et al. [44], de Kruijf et al. [66], He et al. [83]
 GM-CSF Granulocyte macrophage colony-stimulating factor GM-CSF alone did not induce significant mobilization; FLT-3L + GM-CSF synergistically enhanced mobilization. Brasel et al. [22]; Robinson et al. [33]
 PEG-MGDF Pegylated megakaryocyte growth and development factor Multi-day PEG-MGDF alone can induce mobilization; PEG-MGDF synergizes with G-CSF to enhance mobilization. Torii et al. [27], Honda et al. [36]
 SD/01a, IM G-CSFa, and PEGLip-G-CSFa Modified G-CSF Modified G-CSF exhibited superior mobilization potential compared with standard G-CSF De Haan et al. [30], Dygai et al. [62], Yatuv et al. [65]
 GROβ and tGROβb GROβ: CXCL2, a chemokine; tGROβ: truncated form of GROβ (also known as SB-251353, GROβT, GROβ4) Single-dose GROβ or tGROβ alone induced rapid mobilization; tGRO-β synergistically enhanced the mobilization effects of G-CSF, AMD3100, and VLA-4 antagonists. King et al. [37], Pelus et al. [47], Fukuda et al et al. [54], Hoggatt et al. [77], Karpova et al. [107]
 rhPlGF-1 Recombinant human placental growth factor-1 rhPlGF-1 alone had no mobilizing activity; rhPlGF-1 synergized with G-CSF in mobilization. Carlo-Stella et al. [53]
 LECT2 Leukocyte cell-derived chemotaxin 2 5-day LECT2 alone induced mobilization; the combination of LECT2 synergistically enhanced AMD3100 — but not G-CSF-induced mobilization. Lu et al. [91]
 GROα The CXCR2 ligand CXCL1 Single-dose GROα alone induced rapid mobilization, the combination of GROα with CWHM-823 enhanced mobilization. Karpova et al. [107]
 IL-33ab Interleukin-33 3-day IL-33 alone mobilized HSPCs more efficiently than G-CSF or AMD3100; IL-33 additively enhanced G-CSF- and AMD 3100-induced mobilization. Alt et al. [105]
 CSF1-Fc CSF1 Fc fusion protein CSF1-Fc enhanced G-CSF-induced mobilization. Kaur et al. [113]
2. Agents targeting CXCR4/CXCL12 (SDF1) axis
2.1 CXCR4 antagonists
  AMD3100 Plerixafor, a CXCR4 antagonist Single-dose AMD 3100 alone can induce rapid mobilization; AMD 3100 synergizes with G-CSF to mobilize HSPCs. Broxmeyer et al. [48]; Abraham et al. [51], Bonig et al. [61]
  T-140b 4F-benzoyl-TN14003, a highly selective CXCR4 antagonist T-140 has superior mobilization potential than AMD 3100; T-140 synergizes with G-CSF to mobilize HSPCs with higher efficacy than G-CSF + AMD 3100. Abraham et al. [51]
  TG-0054 A novel CXCR4 antagonist Single-dose TG-0054 alone can induce mobilization; TG-0054 showed synergistic effects when combined with G-CSF. Huang et al. [63]
  POL5551b A novel peptidic CXCR4 antagonist Single-dose POL5551 induced higher levels of mobilization than AMD 3100; POL5551 synergizes with G-CSF and CY in mobilization; continuous infusion of POL5551 for 1–2 weeks achieved higher mobilization than G-CSF. Karpova et al. [78], Karpova et al. [94]
  ALT1188 A small molecule CXCR4 antagonist Single-dose ALT1188 alone can induce rapid mobilization; Continuous infusion of ALT1188 for 2 weeks achieved higher mobilization than G-CSF. Karpova et al. [94]
  KRH3955 A chemically distinct CXCR4 antagonist Single-dose KRH3955 alone induced rapid mobilization; the combination of KRH3955 with AMD 3100 did not enhance mobilization. Redpath et al. [97]
  CX0714b A selective and potent CXCR4 antagonist CX0714 has greater mobilization ability than AMD 3100; CX0714 synergistically enhanced G-CSF-induced mobilization with higher efficacy than G-CSF + AMD3100. Wu et al. [103]
  HF51116 A small molecule antagonist of CXCR4 The mobilization efficacy of HF51116 was comparable to AMD 3100; HF51116 synergistically enhanced G-CSF-induced mobilization. Fang et al. [112]
2.2 Other agents targeting CXCR4/CXCL12 axis
  CTCE-0021 An SDF-1 analog Single-dose CTCE-0021 alone can induce rapid mobilization; CTCE-0021 synergizes with G-CSF in mobilization. Pelus et al. [49]
  SCA Sulfated colominic acid, a compound that can modulate CXCR4 function Single-dose SCA alone can induce rapid mobilization; SCA synergizes with G-CSF in mobilization Kubonishi et al. [56]
  ATI-2341 A pepducin CXCR4 agonist Single-dose ATI-2341 alone induced mobilization with similar efficacy to AMD3100 Tchernychev et al. [68]
  APACs (Neo-r9, Neam-r9) and r9 Compounds that can compete with CXCL12 binding to CXCR4 Neo-r9, Neam-r9, and r9 induced robust mobilization similar to AMD3100 when used alone and showed additive effects when combined with AMD3100. Berchanski et al. [69]
  NOX-A12 A mirror-image oligonucleotide inhibitor of CXCL12 Single-dose NOX-A12 exhibits comparable mobilization effects to that of AMD3100; NOX-A12 synergizes with G-CSF to enhance mobilization. Vater et al. [80]
  Me6ab An alkaloid analog that can disrupt the SDF-1α/CXCR4 interaction Single-dose Me6 was more effective in mobilization than AMD3100 or G-CSF alone; Me6 synergized with G-CSF in mobilization with higher efficiency than G-CSF + AMD3100. Zhang et al. [85]
  LGB321 A PIM1 kinase inhibitor that can regulate CXCR4 expression LGB321 enhanced AMD3100-induced mobilization. Müller et al. [109]
3. Agents targeting VLA-4 (α4β1)/VCAM-1 axis
3.1 VLA-4 antagonist
  BIO5192 A VLA-4 antagonist Single-dose BIO5192 alone induced mobilization; BIO5192 enhanced mobilization response when combined with G-CSF, AMD3100, or tGro-β. Ramirez et al. [64], Cao et al. [90], Karpova et al. [107]
  Thioridazine An allosteric antagonist of VLA-4 The mobilizing ability of thioridazine was comparable to AMD3100. Chigaev et al. [70]
  BOP A dual α9β1/α4β1 integrin antagonist Single-dose BOP alone induced rapid mobilization comparable to that induced by AMD3100; BOP synergizes with G-CSF and AMD3100 in mobilization. Cao et al. [90]
  CWHM-823 and -842 VLA-4 antagonists Single-dose CWHM-823 or -842 induced mobilization; the combination of CWHM-823 or -842 with tGro-β enhanced mobilization. Karpova et al. [107]
  Firategrast A VLA-4 antagonist Single-dose firategrast induced mobilization; the combination of firategrast with tGro-β enhanced mobilization. Karpova et al. [107]
3.2 Other agents targeting VLA-4/VCAM-1 axis
  Anti-VCAM-1 Ab Antibody of VCAM-1 Anti-VCAM-1 Ab alone can induce mobilization; the combination of Anti-VCAM-1 Ab with G-CSF increased mobilization. Kikuta et al. [32], Saez et al. [84]
  Bortezomib A proteasome inhibitor that can inhibit transcription and expression of VCAM-1 Single-dose bortezomib induced significant mobilization; Bortezomib enhanced the mobilization effect of G-CSF and AMD-3100. Ghobadi et al. [82]
  Ixazomib A novel proteasome inhibitor that is speculated to modulate VLA4/VCAM1 axis as bortezomib Single-dose ixazomib can induce mobilization; ixazomib synergizes with G-CSF but not AMD3100 to enhance mobilization. Ghobadi et al. [100]
4. Heparan sulfate
 Fucoidan A sulfated polysaccharide that can competitively displace SDF-1 from heparan sulfate proteoglycan anchors. Fucoidan alone induced rapid HSPC mobilization. Fucoidan works synergistically with G-CSF in mobilization. Frenette et al. [31], Sweeney et al. [34], Sweeney et al. [39], Albanese et al. [60]
 EP80031 A heparan sulfate mimetic that can compete with endogenous heparan sulfate. Single-dose EP80031 alone induced rapid mobilization with efficacy comparable to G-CSF and AMD 3100; EP80031 can act synergistically with G-CSF and AMD 3100 to mobilize HSPCs. di Giacomo et al. [72]
 Heparin A pharmacological competitive inhibitor of heparan sulfate Heparin alone only induced modest mobilization; heparin plus G-CSF increased the mobilization of long-term reconstituting and efficient self-renewing cells. Saez et al. [84]
5. Agents targeting purinergic signaling
 AMP, ATP Extracellular nucleotides Combination of AMP with DP induced significant mobilizing effects; ATP enhanced G-CSF- and AMD 3100-induced mobilization Hofer et al. [41], Adamiak et al. [99]
 DP Dipyridamole, a drug inhibiting the cellular uptake of adenosine DP + AMP induced significant mobilizing effects. Hofer et al. [41]
 ARL67156, AMPCP Inhibitor of cell surface ectonucleotidase CD39 or CD73 Both ARL67156 and AMPCP can enhance G-CSF- and AMD 3100-induced mobilization Adamiak et al. [104]
6. Agents inhibiting Cdc42 activity
 Erlotinib An EGFR inhibitor that can reduce Cdc42 activity Erlotinib alone did not induce mobilization; erlotinib enhanced G-CSF-mediated mobilization. Ryan et al. [67]
 ML141 A Cdc42 inhibitor ML141 alone only induced modest mobilization but played a synergistic effect in G-CSF-mediated mobilization. Chen et al. [81]
 CASIN A Cdc42 activity-specific inhibitor Single-dose CASIN alone can induce mobilization; CASIN enhanced G-CSF- and AMD 3100-induced mobilization. Liu et al. [108]
7. Agents targeting sympathetic nervous system signaling
 Desipramine, reboxetine Norepinephrine reuptake inhibitors Desipramine alone did not induce mobilization; desipramine and reboxetine enhanced G-CSF-induced mobilization but did not affect AMD3100-induced mobilization. Lucas et al. [74]
 Adrenaline Catecholaminergic neurotransmitter Adrenaline alone did not induce mobilization; adrenaline enhanced the mobilization efficiency of G-CSF. Chen et al. [75]
 NE Norepinephrine, catecholaminergic neurotransmitter NE alone can induce mobilization; NE enhanced AMD3100-induced mobilization. Dar et al. [71]
8. Agents targeting S1P signaling
 SEW2871 A S1PR1 agonist SEW2871 alone did not induce mobilization; administration of SEW2871 enhanced AMD3100- but not G-CSF-mediated mobilization. Juarez et al. [73], Ogle et al. [96]
 VPC01091 A selective S1PR3 antagonist VPC01091 alone can induce mobilization; VPC01091 enhanced AMD3100-mediated mobilization. Ogle et al. [96]
 THI An inhibitor of sphingosine phosphate lyase THI enhanced mobilization induced by G-CSF and AMD3100. Adamiak et al. [93]
 SLM6031434 An inhibitor of sphingosine kinase type 2 SLM6031434 enhanced mobilization induced by G-CSF and AMD3100. Adamiak et al. [93]
 Anti-CD69 Ab An antibody of CD69 that can increase S1PR1 expression Anti-CD69 Ab induced mobilization of the same magnitude as AMD3100 but did not synergize with AMD3100. Notario et al. [102]
9. Other agents
 CY, paclitaxel and docetaxel Chemotherapeutic agents Priming with cyclophosphamide, paclitaxel, or docetaxel induced mobilization and enhanced G-CSF-induced mobilization. Neben et al. [19], Verma et al. [29], Ojeifo et al. [43]
 PGG-glucan A polysaccharide Single-dose PGG-glucan alone can induce mobilization; PGG-glucan enhanced G-CSF-mediated mobilization. Patchen et al. [26], Cramer et al. [28]
 ProGP Progenipoietin-1, an agonist of both the G-CSF and FLT-3 receptors ProGP-mobilized cells exhibited greater spleen colony-forming activity and competitive repopulating activity than that of G-CSF. Fleming et al. [35]
 Defibrotide A polydeoxyribonucleotide Defibrotide alone had no mobilizing activity, addition of defibrotide significantly enhanced G-CSF-induced mobilization. Carlo-Stella et al. [38]
 α-LFA-1, α-Mac-1 Antibody of β2 integrin LFA-1 or Mac-1 The antibodies themselves had no mobilizing capacity; α-LFA-1 and α-Mac-1 increased G-CSF-induced mobilization. Velders et al. [40]
 Anti-CD49d Ab Antibody of CD49d 5-day anti-CD49d Ab alone can induce mobilization; anti-CD49d Ab enhanced G-CSF-induced mobilization. Liu et al. [45]
 s-kit A soluble form of c-kit receptor s-kit alone can induce mobilization; s-kit increased G-CSF-induced mobilization. Nakamura et al. [46]
 uPAR84-95 A derived chemotactic peptide of the cleaved forms of soluble uPAR 2-day uPAR84-95 exhibited mobilization potency similar to that of 5-day G-CSF; uPAR84-95 did not act synergistically or additively with G-CSF. Selleri et al. [50]
 VTP195183 A RARα specific agonist VTP195183 alone did not induce mobilization; VTP195183 synergizes with G-CSF to enhance mobilization. Herbert et al. [55]
 Anti-Notch2 Ab Antibody of Notch2 Single-dose anti-Notch2 Ab enhanced G-CSF- and AMD3100-induced mobilization. Wang et al. [98]
 PTH Parathyroid hormone 6-day PTH alone can induce mobilization; a combination of PTH and G-CSF showed slight additional effects. Brunner et al. [57]
 Tenecteplase, microplasmin Thrombolytic agents Tenecteplase and microplasmin enhanced G-CSF-induced mobilization. Tjwa et al. [59]
 OTR4120, OTR4131 Glycosaminoglycan mimetics Single-dose OTR4120 or OTR4131 can induce mobilization as effectively as G-CSF and AMD3100; they synergize with G-CSF or AMD3100 in mobilization. Albanese et al. [60]
 Im-HD Immobilized hyaluronidase The native hyaluronidase and Im-HD alone did not induce significant mobilization; Im-HD enhanced G-CSF-induced mobilization. Dygai et al. [76]
 Meloxicam, indomethacin NSAIDs Meloxicam or indomethacin alone can induce mobilization; meloxicam and indomethacin enhanced G-CSF- and AMD 3100-induced mobilization. Hoggatt et al. [101]
 AH23848 and L-161,982 EP4 receptor antagonists Co-administration of AH23848 or L-161,982 with G-CSF significantly enhanced mobilization. Hoggatt et al. [101]
 UDP-G Uridine diphosphate-glucose UDP-G showed comparable mobilizing ability to G-CSF; the combination of UDP-G and G-CSF enhanced mobilization. Kook et al. [79]
 FG-4497 A HIF-1α PHD inhibitor FG-4497 alone did not induce mobilization; FG-4497 synergizes with G-CSF and AMD 3100 to enhance mobilization. Forristal et al. [86], Nowlan et al. [95], Bisht et al. [106]
 CasNa Sodium caseinate Four-dose CasNa induced significant mobilization. Santiago-Osorio et al. [87]
 SnPP Tin protoporphyrin IX, an inhibitor of HO-1 SnPP significantly increased G-CSF- and AMD 3100-induced HSPC mobilization. Wysoczynski et al. [88]
 HS6101 A small molecule lipopeptide Single-dose HS6101 alone can induce mobilization. Xing et al. [89]
 Dexamethasone Glucocorticoid Dexamethasone enhanced AMD3100-induced mobilization. Yan et al. [92]
 Viagra Sildenafil citrate Single-dose Viagra did not induce mobilization, but significantly improved AMD3100-induced mobilization. Smith-Berdan et al. [110]
 CoPP Cobalt protoporphyrin IX 5-day CoPP induced mobilization more efficiently than G-CSF. Szade et al. [111]
  1. aAgents with superior mobilization potentials compared with G-CSF
  2. bAgents with superior mobilization potentials compared with AMD3100
  3. Abbreviations: AMP adenosine monophosphate, ATP adenosine triphosphate, Cdc42 Cell division control protein 42, CSF1 Colony-stimulating factor 1, CXCR-4 C-X-C chemokine receptor type 4, CY cyclophosphamide, EGFR Epidermal growth factor receptor, EP4 E-proteinoid 4, G-CSF Granulocyte colony-stimulating factor, HIF-1α Hypoxia-inducible transcription factor 1α, HO-1 Heme oxygenase 1, HSPCs hematopoietic stem and progenitor cells, LFA-1 Leukocyte function antigen-1, Mac-1 macrophage antigen-1, NSAIDs nonsteroidal anti-inflammatory drugs, PHD Prolyl hydroxylase domain enzyme, PIM1 Proviral integration site for Moloney murine leukemia virus, RARα Retinoic acid receptor alpha, SDF-1 Stromal cell-derived factor-1, S1PR1 Sphingosine-1-phosphate receptor 1, S1PR3 Sphingosine-1-phosphate receptor 3, THI Tetrahydroxybutylimidazole, uPAR urokinase receptor, VCAM-1 Vascular cell adhesion molecule-1, VLA-4 Very late antigen-4