Table 2 Characteristics of included studies evaluating the efficacy and safety of stem cell therapy for patients with Crohn’s disease

Burt et al. 2010 [9]

Y

HSCs

S

2. 10E6/kg

CDAI, CSI

CDAI <150

-

Clinical: 24 (6–12 m)

1 not related

11

9% (12 m)

CSI <12

37% (24 m)

Asymptomatic with no IM

43% (36 m)

Cassinotti et al. 2012 [43]

Y

HSCs

S

Unknown

CDAI

-

-

Clinical: 10 (3 m)

None

-

20% (12 m)

Endoscopic: 5 (3 m)

50% (24 m)

Hasselblatt et al. 2012 [10]

Y

HSCs

S

Unknown

CDAI

CDAI <150

-

Clinical: 5 (6 m)

4 related

-

7 (37.2 m)

Endoscopic: 5 (6 m)

Fever, renal failure

Hawkey et al. 2015 [13]

Y

HSCs

S

3 ~ 8.10E6/kg

CDAI

Sustained disease remission:

-

2/23 versus 1/22 (12 m)

76 versus 38 related

9 SAEs in 5 patients undergoing HSCT:

-

(ASTIC)

1) CDAI <150 for >3 m

10 versus 2 (1 year)

3 EBV reactivation, 2 CMV reactivation,

2) No active treatment in the last 3 m

1 herpes zoster, 1 BK virus, 1 intestinal adenovirus, 1 VZV

3) No mucosal erosion or ulceration in GI tract

8 neutropenic sepsis

Onken et al. 2006 [27]

N

Prochymal™

S

Unknown

CDAI

-

Clinical: 9/3 (14 d)

1 unrelated

None

-

Duijvestein et al. 2010 [29]

Y

BMSCs

S

2 × 1/2.10E6/kg

CDAI, CDEIS

Remission: CDAI <150

-

Clinical: 3/0 (6 w)

None

None

-

Response: a drop in CDAI >70

Endoscopic: 2/0 (6 w)

Lazebnik et al. 2010 [30]

N

BMSCs

S

150–200.10E8

CDAI, RCAI, Mayo, and Gebs scales

-

-

Clinical: 11/0 (4–8 m, CD)

-

None

-

39/0 (4–8 m, UC)

Forbes et al. 2014 [36]

N

BMSCs

S

4 × 2.10E6/kg

CDAI, CDEIS

Remission: CDAI <150

-

Clinical: 12/8 (42 d)

1 unrelated

1 gastroenteritis

-

Endoscopic improvement: CDEIS <3 or a decrease by >5

Endoscopic: 7/0 (42 d)

Dhere et al. 2016 [40]

Y

BMSCs

S

2/5/10.10E6/kg

CDAI

Response: CDAI + CRP

-

Clinical: 5/- (2 w)

7

1 acute appendicitis

-

2 related

1 C. difficile colitis

Garcia-Olmo et al. 2005 [16]

Y

ASCs

L

Unknown

Fistula closure

-

N

8 fistulas in 4: 2/6 (8 w)

None

None

-

Garcia-Olmo et al. 2009 [28]

Y

ASCs + Fg:25 (7 CD)

L

20/60.10E6

Fistula closure

-

N

ASCs + Fg: -/1 (7 CD, 8 w)

None

Perianal sepsis: ASC group (n = 3, 12%) versus Fg alone (n = 9, 36%) (P = 0.04).

Group B: 3 (12 m)

Fg:24 (7 CD)

Fg: 2/5 (7 CD, 8 w)

No data for CD

Ciccocioppo et al. 2011 [31]

Y

BM-MSCs

L

50.10E6

Complete closure

CDAI + PDAI

Y

3/7 (12 m)

None

None

None (12 m)

Park et al.2012 [32]

Y

ASCs + Fg

L

1 ~ 4.10E7

Fistula healing

-

N

-/9 (8 w)

-

-

-

de la Portilla et al. 2013 [34]

N

ASCs

L

20/60.10E6

Fistula closure

-

Y

23 fistulas in 22: 5/18 (6 m)

2

Infections and infestations 9/7

-

Anal abscess 5/4

Anal fistula infection 2/2

Cho et al. 2013 [33]

Y

ASCs

L

10/20/40.10E6

Fistula healing

-

N

1/3 (2 m)

None

3 enterocolitis

3 (8 m)

Lee et al. 2013 [35]

Y

ASCs

L

30/60.10E6

Fistula healing

-

N

5/27 (2 m)

None

No ASC-related AEs

3 (12 m)

1 grade 4 peritonitis caused by CD

Park et al. 2014 [37]

N

ASCs

L

10/30.10E6

Complete closure

-

N

-/1 (8 w)

-

-

-

-/3 (8 m)

Cho et al. 2015 [38]

Y

ASCs

L

30/60.10E6

Fistula healing

-

N

28/35 (12 m)

None

None

3/26 (12 m)

27/36 (24 m)

4/24 (24 m)

Molendijk et al. 2015 [39]

Y

BMSCs (n = 15)

L

10/30/90.10E6

Fistula healing

-

Y

8 versus 1 (week 6)

None

None

-

Placebo

7 versus 2(wk 12)

(n = 6)

9 versus 2 (week 24)

Lightner et al. 2016 [41]

Y

ASCs

L

Unknown

Fistula healing

-

Y

6/6 (6 m)

-

-

-

Panés et al. 2016 [42]

N

ASCs (Cx601)

L

120.10E6

Combined remission

-

Y

53/107 versus 36/105

SAE: 18/103 versus 14/103

Anal abscess (6 versus 9)

-

Saline

SAE related: 5/103 versus 7/103

Proctalgia (5 versus 9)