TABLE 1.

WJ‐MSC infusions and clinical applications in haematology (cord blood MSCs excluded)

Indications	Authors Country	Number of patients/ Phase Trial	Infusion dose	Schedule	Results	Side effects
GVHD Treatment	Soder et al 50 USA	N = 10, adults Phase 1	2 or 10 × 106 MSCs/kg/infusion	2 infusions: on day 0 and 7 of aGVHD treatment	ORR 70%, CR 40%, PR 30%	No acute infusion‐related toxicity No treatment‐related adverse events (TRAE) a No ectopic tissue formation
	Wu et al 54 China	N = 24 phase 2	0.6 × 106/kg Range (0.5–1.0) ×106/kg	Single infusion Refractory aGVHD and cGVHD	55.6% of improvements for skin, 100% for oral mucosa, 37.5% for GI tract, no response for liver and lung	No acute infusion‐related toxicity No TRAE a
GVHD Prophylaxis	Zhu et al 51 China	N = 25, children Phase 1–2	Mean = 1.14 × 106 MSCs/kg Range (1.03–1.39) ×106/kg	Single infusion 1 hour before HSCT	2 patients severe late onset aGVHD 2 patients extensive cGVHD	No acute infusion‐related toxicity Adverse events:CMV infection in 23 patients, bacterial and fungal infections, treatment related?
	Wu et al 52 China	N = 50 Phase 2	Mean = 5 × 105 MSCs/kg	Single infusion 4 hours before HSCT	12/50 aGVHD gr II‐IV 3 extensive cGVHD	No acute infusion‐related toxicity TRAE a observed in 9 patients
	Gao et al 53 China	N = 124 Multicentre, double‐blind, randomized Phase 2	Mean = 3 × 107/100 ml/month Range?	Repeated infusions 1/month ×4 >4 months after HSCT	3/62 severe cGVHD versus 8/62 in the control group cGVHD = 27.4% in the MSCs group versus 49% in the control group (p = 0.021)	No acute infusion‐related toxicity No increase in adverse events a : infections and grade 1–2 liver dysfunction and renal impairment observed in 45 patients (72.6%) in the MSCs group and 40 patients (64.5%) in the non‐MSC group
Engraftment and GVHD	Wang et al 37 China	N = 22, SAA Phase 1–2	Mean = 1.2 × 106 MSCs/kg Range (0.27–2.5) ×106/kg	Single dose 4 hours before HSCT	22 engraftments, no severe aGVHD nor cGVHD Long‐term full donor chimerism for 21/22 patients	Two patients had slight fever immediately after cell injection, which resolved within 12 hours. No TRAE a
	Li et al 38 China	N = 17, SAA adults Phase 1–2	Mean = 4 × 106 MSCs/kg Range (2.87–10) ×106/kg	Single infusion 6 hours before HSCT	16/17 engraftments with full donor chimerism, 1/17 graft failure 4/17 grade III‐IV aGVHD 6/17 cGVHD (1 severe)	No acute infusion‐related toxicity Adverse events: CMV and/or EBV infections in 10 patients. Treatment related?
	Wang et al 39 China	N = 17, SAA Children Phase 1–2	Median dose 4 × 107 (0.5–8)	Single infusion On day +1 after HSCT	17/17 myeloid engraftments 16/17 platelet engraftments 1 grade III‐IV aGVHD cGVHD = 21.2% 1 secondary graft failure OS = 71%	No acute infusion‐related toxicity Adverse events were not related to MSC infusion: Three patients died of TRM, because of infection on day +36, severe aGVHD on day +44 and viral interstitial pneumonia on day +634
	Wu et al 36 China	N = 20 (8 patients in the MSC group) Cord blood transplantation Randomized phase 2	Median dose of 7.19 × 106 MSCs/kg (2.44–10.12)	Single infusion 4 hours before Cord blood	Faster recovery of ANC (p = 0.003) and platelets (p = 0.004) in the MSC group	No acute infusion‐related toxicity No ectopic tissue on MRI and PET survey in the interval of 3 months after WJ‐MSCs infusion. No CMV disease, septic shock, nor fungal infection. TRAE a observed in 5 patients (4 mild GVHD and 1 relapse). No deaths related to treatment toxicity. (2 deaths related to infections, and 2 relapses in the comparative group)
	Wu et al 40 China	N = 21, SAA Phase 1–2	5 × 105 MSCs/kg Invariable dose	Single infusion 4 hours before HSCT	21/21 sustained engraftments 2‐y PFS = 74% 5 grade III–IV aGVHD 3 extensive cGVHD	No acute infusion‐related toxicity TRAE a observed in 4 patients

Abbreviations: cGVHD, chronic GVHD); CMV, cytomegalovirus; CR, complete response; EBV, Epstein‐Barr virus; GI, gastrointestinal; GVHD, graft versus host disease (aGVHD, acute GVHD; ORR, overall response; PFS, progression‐free survival.; PR, partial response; SAA, severe aplastic anaemia.

^a Treatment‐related adverse events (TRAE) were graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE version 4.0) and commonly include oral ulcer, diarrhoea, gastrointestinal haemorrhage, haemorrhagic cystitis, interstitial pneumonia, and liver or renal dysfunction, and, rarely, relapse and GVHD.