Table 1 Clinical application of bone marrow mesenchymal stem cells in regenerative medicine

ALS

I.T

26

15 ± 4.5 × 10⁶ cell

BMSC

I/IIa

No

ALSFRS were significantly reduced. FVC and WSs were stable in patients

N/A

[71]

ALS

I.T

10

N/A

BMSC

I

No

MRI showed no structural changes (including tumor formation) in either the brain or the spinal cord. However, the lack of postmortem material prevents any definitive conclusion about the vitality of the MSCs after transplantation

N/A

[72]

ALS

I.T

15

10 × 10⁶ cell

BMSC

N/A

No

Reducing of the disease was indicated following MSCs therapy

N/A

[73]

ALS

I.M

I.M and I.T

12

14

1 × 10⁶ cell

1, 1.5 and 2 × 10⁶ cell I.T

24, 36 and 48 × 10⁶ cell I.M

MSC-NTF

I/II

IIa

No

The rate of progression of the FVC and ALSFRS was reduced. The results suggest that IT and IM administration of MSC-NTF cells in patients with ALS is safe and provide indications of possible clinical benefits

NCT01051882

NCT01777646

[74]

ALS

I.T

8

1 × 10⁶/kg

BMSC

I

No

There was no acceleration in the reduction in the ALSFRS-R, Appel ALS score, and FVC. Elevation of TGF-β and IL-10. Reduction in MCP-1

NCT01363401

[75]

ALS

I.T

27

1 × 10⁷–10⁸ cell

Adipose MSC

I

No

Elevation of CSF protein and nucleated cells along with MRI of thickened lumbosacral nerve roots

N/A

[76]

ALS

I.T

67

30 × 10⁶ cells

WJ-MSC

N/A

No

Median survival time increased twofold in patients

N/A

[77]

PD

I.A

5

N/A

BMSC

I

No

Autologous BMSCs is safe and reduce disease progression

NCT01824121

[78]

PD

I.A

5

1.2–2 × 10⁶/kg

BMSC

II

No

Participants were alive and motor function rating scales remained stable for at least 6 months during the 12-month follow-up period

NCT01824121

[79]

PD

I.T

7

1 × 10⁶/kg

BMSC

N/A

No

Improvement was found in symptoms like facial expression, gait, and freezing episodes

N/A

[80]

SCI

I.T

3

15 × 10⁶ cell

BMSC

I

No

No improvement in their sensory scores without any changes in the AIS and SCIM-III scores. No motor recovery was observed in any of the participants

N/A

[81]

SCI

I.V

13

0.84–1.6 × 10⁸ cell

BMSC

II

No

ASI, ISCSCI-92, and SCIM-III functional improvements after MSC injection

N/A

[82]

SCI

I.T

6

1.2 × 10⁶/kg

BMSC

I

No

MSCs can be safely administered through intrathecal injection in spinal cord injury patients

NCT02482194

[83]

SCI

Interalesion

14

1 × 10⁷ cell

BMSC

I

No

Improvements in tactile sensitivity and eight participants improved lower limbs motor functional gains, chiefly in the hip flexors and developments in urologic function

NCT01325103

[84]

SCI

subarachnoid

10

3 × 10⁷ cell

BMSC

II

No

Improvement in bladder compliance and active muscle reinnervation

NCT0216590

[85]

SCI

I.T

9

10 × 10⁷ cell

BMSC

II

No

Improve sensitivity, motor power, spasms, spasticity, neuropathic pain, sexual function or sphincter dysfunction in the SCI patients

NCT02570932

[86]

SCI

I.T

14

9 × 10⁷ cell

Adipose MSC

N/A

Yes

Several patients showed mild improvements in neurological function

N/A

[87]

SCI

I.T

10

10 × 10⁶ cells

WJ-MSC

I/IIa

No

Significant improvement in pinprick sensation. Increase in bladder maximum capacity

NCT03003364

[88]

Stroke

I.V

31

N/A

BMSC

N/A

No

Improvements in NIHSS score, motor-Fugl-Meyer scores, and task-related functional MRI activity in motor cortex-4a. There were no remarkable progresses in Barthel Index, NIHSS, and modified Rankin scores

NCT 00,875,654

[89]

Stroke

I.V

15

21

0.5, 1.0, and 1.5 × 10⁶/kg

1.5 × 10⁶/kg

BMSC

I

II

No

Barthel Index scores increased. Electrocardiograms, laboratory tests, and computed tomography scans of chest/abdomen/pelvis suggesting that BMSCs could alleviate the stroke

NCT01297413

[90]

Stroke

Stereotactic

10

20–50 × 10⁶ cell

BMSC

I

No

Improvement in the motor function

N/A

[91]

Stroke

I.V

17

2 × 10⁶/kg

BMSC

II

No

NIHSS score, modified Rankin Scale or Barthel Index did not improve after the transplantation. There was an improvement in absolute change in median infarct volume

NCT01461720

[92]

Primary biliary cirrhosis

I.V

7

0.5 × 10⁶ /kg

UC-MSC

N/A

No

Reduction in ALP and GGT. UC-MSC therapy is feasible and well tolerated in patients with primary biliary cirrhosis

NCT01662973

[93]

Ischemic-type biliary lesions

I.V

12

1 × 10⁶/kg

UC-MSC

I

No

Reduction in ALP, GGT, and total bilirubin

NCT02223897

[94]

ACLF

I.V

9

1 × 10⁶/kg

BMSC

I/II

No

Improvement in CP, MELD, and ACLF

N/A

[95]

ACLF

I.V

110

1–10 × 10⁵/kg

BMSC

N/A

No

Improvement in serum total bilirubin, and MELD scores. Enhancing liver function and reducing the prevalence of severe infections

NCT01322906

[96]

Severe liver disease

I.A

58

0.47 ± 0.15 × 10⁸/kg

BMSC

N/A

No

Expansion of macrophages concurrent with an upregulated expression of genes involved in inflammatory and regenerative pathways. With the negative results from the clinical trial, the impact of the liver stem cell therapy has to be interpreted as weak

N/A

[97]

Alcoholic cirrhosis

I.A

72

5 × 10⁷ cell

BMSC

II

No

Reduction in the proportion of collagen. Improvement in Child–Pugh scores

NCT01875081

[98]

ARVD

I.A

39

1, 2.5 and 5.0 × 10⁵ cells/kg

Adipose MSC

Ia

No

Increase renal blood flow. Reduction in hypoxia, renal vein inflammatory cytokines, and angiogenic biomarkers

NCT02266394

[99]

ADPKD

I.V

6

2 × 10⁶/kg

BMSC

I

No

eGFR value declined and the level of serum creatinine enhanced

NCT02166489

[100]

CKD

I.V

7

1–2 × 10⁶ /kg

BMSC

I

No

Variations in eGFR and serum creatinine were not statistically significant

NCT02195323

[101]

AKI

I.V

16

250 × 10⁶ cell

BMSC

I/II

No

Stimulates an immunotherapeutic response that initiates an enhanced phenotypic alteration from tissue injury to tissue repair

NCT 03,015,623

[102]

Ischemic

Intramyocardial

60

77.5 ± 67.9 × 10⁶ cell

BMSC

II

No

Left ventricular end-systolic volume was significantly reduced; also LVEF, stroke volume, and myocardial mass remarkably improved

NCT00644410

[103]

Ischemic

Intramyocardial

14

15 × 10⁷ cell

BMSC

I

No

Quality of life was improved along with a substantial decrease in angina scores

NCT01557543

[104]

Ischemic

TESI

125

15 × 10⁷ cell

BMSC

II

No

Quality of life was significantly improved by MSCs. LEVF, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups

NCT02501811

[105]

Ischemic

I.V

13

1 × 10⁶/kg

Adipose MSC

IIa

No

No efficacy end points were remarkable between treatment groups; however, a trend toward improvement was observed in the NIHSS scores

NCT01678534

[106]

AMI

Intracoronary

116

6 × 10⁶ cell

WJ-MSC

N/A

No

Increase in the myocardial viability and perfusion within the infarcted territory. Increase in the LVEF

NCT01291329

[107]

AMI

N/A

100

100 × 10⁶ cell

BMSC

II

No

Improvement in cardiac function, induction of remodeling and regeneration, and improvement in quality of life

NCT03047772

[108]

HF

I.V

30

1 × 10⁶/kg

UC-MSC

I/II

No

Reduction in ejection fraction. Improvements in left ventricular function, functional status, and quality of life

NCT01739777

[109]

HF

N/A

8

1.2–6.5 × 10⁷ cell

BMSC

N/A

No

There were no major differences in B-type natriuretic peptide, LVEF, and peak oxygen uptake at 2 months

N/A

[110]

NIDCM

TESI

34

N/A

BMSC

I/II

No

MSC therapy improves a variety of parameters in NIDCM irrespective of patient sex

N/A

[111]

NIDCM

TESI

37

10 × 10⁷ cell

BMSC

I/II

No

Minnesota Living with Heart Failure Questionnaire score decreased. The Major Adverse Cardiac Event rate was lower in allo vs. auto. Also, TNF-α decreased, to a greater extent in allo vs. auto at 6 months

NCT01392625

[112]

HLHS

Intramyocardial

30

2.5 × 10⁵ /kg

BMSC

I/II

No

This study was determined the safety, feasibility, and usefulness of MSC administration into the left ventricular myocardium

NCT02398604

[113]

DCM

Intracoronary

53

4.9 ± 1.7 × 10⁸ cell

BMSC

N/A

No

LVEF, NYHA class, and myocardial perfusion had improved significantly in the BMSC group; however, LVEDd remained unchanged

N/A

[114]

Refractory angina

Intramyocardial

60

N/A

Adipose MSC

N/A

No

Patients receiving ASCs had improved cardiac symptoms and unchanged exercise capacity

NCT01449032

[115]

OA

Intra-articular

12

1, 10 and 50 × 10⁶ cell

BMSC

I/II

No

Improved KOOS pain, symptoms, quality of life, and WOMAC. The levels of pro-inflammatory monocytes/macrophages and IL-2 reduced in the synovial fluid after intervention

NCT02351011

[116]

OA

Subchondral

140

7800 MSCs/mL in 20 ml

BMSC

N/A

No

MSCs had a significant effect on pain to postpone or avoid the TKA in the contra lateral joint of patients with OA

N/A

[117]

OA

Intra-articular

60

5727 MSCs/mL in 40 ml

BMSC

N/A

No

Implantation of MSCs in the subchondral bone of an osteoarthritic knee is more effective to postpone TKA than injection of the same intra-articular dose in the contralateral knee

N/A

[118]

OA

Intra-articular

60

100 × 10⁶ cell

BMSC

II

No

Treatment with BMSC related to platelet-rich plasma was demonstrated to be a feasible alternative treatment for individuals with OA

NCT02365142

[119]

OA

Intra-articular

30

10 or 100 × 10⁶ cell

BMSC

I/II

No

BMSCs together with hyaluronic acid is a safe and viable process that leads to a clinical and functional improvement in knee OA

NCT02123368

[120]

OA

Intra-articular

18

N/A

BMSC

N/A

Yes

Improve the pain, function and daily living activities and quality of life subscales

N/A

[121]

OA

Intra-articular

13

61 ± 0.6 × 10⁶ cell

BMSC

I/II

No

Normalized KOOS improved significantly. Mean knee cartilage thickness measured by MRI improved significantly

NCT02118519

[122]

OA

Intra-articular

18

2, 10, 50 × 10⁶ cell

Adipose MSC

I

No

Significantly improved pain levels and function

N/A

[123]

OA

Intra-articular

30

100 × 10⁶ cell

Adipose MSC

I

No

MRI Osteoarthritis Knee Score indicated modification of disease progression and improved pain levels and function

N/A

[124]

OA

Intra-articular

12

1 × 10⁸ cells

Adipose MSC

IIb

No

Significant improvement in the WOMAC score. Provided satisfactory functional improvement and pain relief for patients

N/A

[125]

OA

Intra-articular

40

20 × 10⁶ cell

UC-MSC

I/II

No

Significantly improved pain levels and function. Pain Visual Analog scale was significantly lower in the MSC group

NCT02580695

[126]

OA

N/A

29

1 × 10⁶ cell

UC-MSC

N/A

No

Visual analog scale showed decreased pain. MSC Decreased WOMAC score

NCT03800810

[127]

Bone fracture

Percutaneous

22

50–100 × 10⁶ cell

BMSC

I/II

No

TUS, GDE score was improved and pain at palpation at the fracture site was reduced

NCT02020590

[128]

Bone fracture

Intramedullary

I.V

20

4 × 10⁷ cells

2 × 10⁸ cells

WJ-MSC

I/IIa

No

VAS, ODI, and SF-36 scores significantly improved. Promoted bone architecture

N/A

[129]

Mandibular lesions

Intralesional

20

N/A

BMSC

N/A

No

Increase in bone density with respect to the baseline levels. The percent of reduction in the defects’ size was significantly higher compared with control

N/A

[130]

Wound healing

Intralesional

8

1 × 10⁶ cell

BMSC

N/A

No

Reduction in ulcer size or complete wound closure

N/A

[131]

Wound healing

N/A

316

N/A

Adipose MSC

N/A

No

Granulation tissue coverage rate and thickness of granulation tissue were significantly improved

N/A

[132]

Diabetic foot ulcers

N/A

59

1 × 10⁶ cells

Adipose MSC

N/A

No

Complete wound closure was achieved for 82% at week 12. Kaplan–Meier median times to complete closure were reduced

NCT02619877

[133]

Diabetic foot ulcers

Endovascular

53

4.8 to 8.6 × 10⁷ cell

UC-MSC

N/A

No

Significant increase in neovessels, accompanied by complete or gradual ulcer healing

N/A

[134]

Diabetic foot ulcers

N/A

114

N/A

Autologous micro-fragmented adipose tissue

N/A

No

The skin tropism was improved in the treatment group

NCT03276312

[135]

Uterine injury

Intrauterine

10

N/A

UC-MSC

I

No

The volume of the uterus, and cesarean scar diverticulum showed an improving tendency

NCT03386708

[136]

Vocal fold

Local injection

16

0.5–2 × 10⁶ cell

BMSC

I/II

No

Voice Handicap Index was meaningfully enhanced

NCT01981330

[137]