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Table 1 Experimental models used to study cell-based products in the treatment of VF scarring

From: Stem cell therapy for vocal fold regeneration after scarring: a review of experimental approaches

 

Animals (n)

Surgery type

Time after surgery before IMP, days

Cell type/carrier

Dose

Duration

Use of IS

Kanemaru et al. [49]

Rats (4)

Exterior access

Injury with a 32G needle

0

Xenogeneic (murine) BM-MSC expressing GFP

(1–3) × 105

8 weeks

No

Hertegard et al. [23]

Rabbits (10)

Endolaryngeal

Limited unilateral resection of VF with microforceps and microscissors

0

Xenogeneic (human) BM-MSC

0.8 × 105 cells in 0.1 mL

4 weeks

Yes, Tacrolimus

Lee et al. [45]

Dogs (10)

Endolaryngeal

Bilateral resection of the posterior third of VF with an electrocoagulator

4

Autologous AD-MSC/atelocollagen

(1.0–3.0) × 106 cells in 0.2 mL

8–24 weeks

No

Johnson et al. [52]

Nude rats (12)

Endolaryngeal

Bilateral injury of the middle third of VF with a 27G needle

30

Xenogeneic (murine)

BM-MSC expressing GFP/HA-based sECM

ND

4 weeks

No

Xu et al. [46]

Rabbits (40)

Endolaryngeal

Limited resection of the anterior and middle third of VF

3–5

Autologous AD-MSC/collagen or HA

ND

15, 40 days and 3, 6, and 12 months

No

Svensson et al. [37]

Rabbits (12)

Endolaryngeal

Limited bilateral VF resection using microforceps

63

Xenogeneic (human) BM-MSC

(0.8–1.0) ˣ 105 cells in 0.1 mL

10 weeks

Yes, Tacrolimus

Ohno et al. [50]

Dogs (12)

Endolaryngeal

Bilateral VF resection using microforceps and microscissors

60

Autologous AD-MSC/atelocollagen sponge

1 × 106 cells in 5 × 3 × 3-mm

6 months

No

Kim et al. [60]

Rabbits (24)

Endolaryngeal

Local uni/ bilateral VF resection using microinstruments

0

Xenogeneic (murine) BM-MSC expressing GFP

1 × 105 cells in 50 μL

3 months

No

Kim et al. [38]

Rabbits (40)

Endolaryngeal

Local uni/ bilateral VF resection using microinstruments

0

Xenogeneic (human) AD-MSC/Alginate-HA hydrogel

1 × 106 cells in 50 μL

3 months

No

Peng et al. [27]

Dogs (14)

Endolaryngeal

Bilateral resection of the middle third of VF using a laser

0

Allogeneic

MSC from epiglottis mucosa/collagen

2 × 106 cells in 0.2 ml

2–8 weeks

No

Choi et al. [25]

Rabbits (24)

Endolaryngeal

Bilateral VF injury with an electrocoagulator

0

Xenogeneic BM-MSC/Small intestine submucosa

2 × 107 cells in 50 μL

8 weeks

No

Hu et al. [39]

Dogs (17)

Endolaryngeal

Limited resection of the anterior and middle thirds of VF

ND

Autologous AD-MSC, vocal fold fibroblasts, differentiated AD-MSC

(3.0–4.0) × 105 cells in 3–4 ml

15 and 40 days and 3 and 6 months

No

Hiwatashi et al. [40]

Rats (70)

Endolaryngeal

Limited unilateral VF resection using microscissors

60

Allogeneic

AD-MSC and BM-MSC

5.0 × 105 cells in 50 μL

1 and 3 months

No

Svensson et al. [57]

Rabbits (16)

Endolaryngeal

Limited unilateral VF resection using microforceps

0

Xenogeneic (human) ESC

104 cells in 0.1 mL

6 weeks, 3 months

Yes, Tacrolimus

Valerie et al. [53]

Rabbits (74)

Endolaryngeal

Limited bilateral resection of the anterior and middle thirds of VF using microforceps

540 (18 months)

Autologous AD-MSC

1.0 × 104 cells in 0.1 mL

3 months

No

De Bonnecaze et al. [41]

Rabbits (20)

Exterior (median thyroidotomy)

Unilateral injury of left VF with an electrocoagulator

0

Autologous AD-MSC

2 × 106 cells in 0.1 mL

6 weeks

No

Shiba et al. [47]

Rabbits (8)

Exterior (midline laryngofissure)

Unilateral removal of the mucosa along the whole VF length

0

Autologous AD-MSC/fibrin gel

NA

4 weeks

No

Imaizumi et al. [26]

Rats (30)

Endolaryngeal

Unilateral VF injury with a 25G needle

0

Xenogeneic human iPSC/HA hydrogel

1.0 × 105 cells in 5 μL

1 and 2 weeks

No

Morisaki et al. [61]

Rats (72)

Endolaryngeal

Unilateral VF injury with a 25G needle

0

Allogeneic

AD-MSC

5.0 × 105 cells in 50 μL

3, 14, 56 days

No

Bartlett et al. [54]

Rabbits (84)

Endolaryngeal

Bilateral resection of the middle VF third using microforceps

42

Xenogeneic (human) BM-MSC/HyStem-VF hydrogel

3 × 105 cells in 100 μL twice or 1.5 × 105 cells in 100 μL

2, 4, and 10 weeks

No

Goel et al. [48]

Rabbits (8)

Exterior (midline laryngofissure)

Unilateral removal of the mucosa along the whole VF length

0

Allogeneic

AD-MSC/fibrin gel

NA

4 weeks

No

Svistushkin et al. [62]

Rabbits (12)

Endolaryngeal

Limited unilateral VF resection using microforceps

84

Autologous BM-MSC

6 × 105 cells in 0.6 mL

12 weeks

No

Hertegård et al. [22]

Rabbits (18)

Endolaryngeal

Limited VF resection using microforceps

0

Xenogeneic (human) BM-MSC/HA hydrogel

1 × 105 cells in 0.1 mL

3 and 25 days

No

  1. AD-MSC adipose tissue-derived mesenchymal stromal cells, BM-MSC bone marrow-derived mesenchymal stromal cells, ESC embryonic stem cells, GFP green fluorescent protein, HA hyaluronic acid, IMP implantation, iPSC induced pluripotent stem cells, IS immunosuppressor, sECM synthetic extracellular matrix, VF vocal folds