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

 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/01^a, IM G-CSF^a, and PEGLip-G-CSF^a

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 tGROβ^b

GROβ: CXCL2, a chemokine; tGROβ: truncated form of GROβ (also known as SB-251353, GROβ_T, GROβ_△4)

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-33^ab

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]

  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-140^b

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]

  POL5551^b

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]

  CX0714^b

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]

  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]

  Me6^ab

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]

  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]

  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]

 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]

 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]

 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]

 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]

 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]

 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]

 uPAR_84-95

A derived chemotactic peptide of the cleaved forms of soluble uPAR

2-day uPAR_84-95 exhibited mobilization potency similar to that of 5-day G-CSF; uPAR_84-95 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]