Table 1 List of key studies utilizing MSCs for treating various clinical conditions

Musculoskeletal Disease

Study Number

Type of MSC used in the study

Main Effect

References

1

UC-MSCs

Stable muscle power after 1-year follow-up. No negative effects

[17]

2

BM-MSCs

Improve tissue repair and protect muscles from damage induced injury

[18]

3

UC-MSCs

IGF-1 and MSCs injection led to efficient repair of muscles in mouse model

[19]

 Muscular Dystrophy

4

UC-MSCs

Myogenic differentiation of MSCs combine with ray myoblasts to form myotubules

[20]

5

P-MSCs

Mice showed increased levels of utrophin and reduced inflammation

[21]

6

BM-MSCs

Dystrophin expression chimeric MSCs increased function and strength of muscle and less immune response

[22]

1

iPSC-derived MSCs

Bone loss reduction and micro vessel density in mouse model

[23]

2

BM-MSCs

Reduced total hip replacement arthroplasty conversion rate

[24]

 Osteonecrosis

3

BM-MSCs

Suppressed adipogenesis and upregulated SOX9

[25]

4

BM-MSCs

Facilitated repair of bone

[26]

5

Rabbit MSCs

MSCs with GFP tag, fluorescence only on the femur

[27]

1

BM-MSCs

Higher bone mineral density and accelerated cranial bone healing

[28]

2

Ad-MSCs and UC-MSCs

Adipose MSCs exhibit higher osteogenic differentiation and higher bone formation rates

[29]

 Cranial Defects

3

UC-MSCs and BM-MSCs

Rats treated with MSC treatment exhibit greater expression of Runx2, collagen I, and osteocalcin

[30]

4

DP-MSCs and BM-MSCs

Dental pulp MSCs exhibit similar properties as BM-MSCs for bone regenerative applications

[31]

5

Ecto-MSCs and BM-MSCs

Ecto-MSCs had a higher number of proliferative cells, but both cells promoted bone regeneration

[32]

1

Ad-MSCs

Osteogenic differentiation and vascularization in non-union fracture models in rats

[33]

2

UC-MSCs

Optimal bone formation in infected non-union fracture in 54 year old patient

[34]

 Non Union Bone Fracture

3

BM-MSCs

BM-MSCs into non-union femur fracture showed bone union in 8 weeks

[35]

4

BM-MSCs

MSCs combined with shock-wave therapy improved fracture stiffness and mechanical strength

[36]

5

BM-MSCs

Exosomes from BM-MSCs enhanced osteogenesis, bone healing, and angiogenesis

[37]

1

BM-MSCs

Hyaluronic acid and BM-MSCs showed MOCART scores than patients with only hyaluronic acid treatment

[38]

 Osteoarthritis

2

Ad-MSCs

Improved pain and knee function of patients with no negative effects

[39]

3

Ad-MSCs

Injection of 10^8 MSCs found effective to reduce osteoarthritis symptoms

[40]

Nervous System Diseases

Study Number

Type of MSC used in study

Main Effect

References

1

UCB-MSC

Activation of microglial cells and prevention of β-amyloid peptide plaques deposition. Induce endogenous neurogenesis

[41]

2

BM-MSC

Ameliorate Alzheimer’s disease through induction of miR-29c-3p and targeting of BACE1

[42]

 Alzheimer’s Disease

3

Unknown source MSC

Promote neurogenesis and relieve Aβ 1–42 induced cognitive impairment

[43]

4

BM-MSC

Reduce astrocytic inflammation and synaptogenesis. Increase expression of microRNA-146a in hippocampus

[44]

5

MB-MSC

Memory and spatial learning improvement. Reduction of tau hyperphosphorylation. Improving of amyloid plaques. Increase in Aβ degrading enzymes and reduction of pro-inflammatory cytokines

[45]

1

UC-MSC

Ameliorate neuroinflammation and locomotor functions. Preservation of intestinal goblet cells

[46]

2

BM-MSC

Reduction in expression of hydroxylase immunoreactive cells and neural loss

[47]

 Parkinson’s Disease

3

WJ-MSC

Restoration of BDNF, NGF, passive avoidance, memory, and hippocampal long-term potentiation

[48]

4

UC-MSC

Reduction in cell apoptosis and loss of dopaminergic neurons

[49]

5

BM-MSC

Increase in the number of TH-positive neuronal cells and fibers

[50]

1

BM-MSC

Slower increment in Unified MSA Rating Scale score

[51]

2

UCB-MSC

Lower Unified MSA Rating Scale score than the control group

[52]

 Multiple System Atrophy

3

BM-MSC

Prevention of neurodegeneration and improvement in behavioral disorders

[53]

4

Ad-MSC

Lower Unified MSA Rating Scale score than control group

[54]

5

BM-MSC

Increase survival rate of nigrostriatal neurons

[55]

1

WJ-MSC

Showed no adverse effects

[56]

2

BM-MSC or Ad-MSC

Lowered ALS Functional Rating Scale-Revived score and the forced vital capacity

[57]

 Amyotrophic Lateral Sclerosis

3

WJ-MSC

Increase in survival time

[58]

4

BM-MSC

Reduction of ALS Functional Rating Scale. Increase in anti-inflammatory and decrease in pro-inflammatory cytokines

[59]

5

BM-MSC

Improvement in neurodegeneration, neuroinflammation, and neurotrophic factors

[60]

1

UC-MSC

Improved sensory functions and mobility

[61]

2

UC-MSC

Improved motor and sensory functions

[62]

 Spinal Cord Injury

3

Ad-MSC

Improved motor and sensory functions

[63]

4

BM-MSC

Showed no adverse effects

[64]

5

UC-MSC

SCI recovery and nerve growth factor production

[65]

Cardiovascular Diseases

Study Number

Type of MSC used in the study

Main Effect

References

1

Unknown source MSCs

Extracellular vesicles restored right ventricular systolic pressure to baseline

[66]

2

iPS-MSCs

Extracellular vesicles reduced arterial stiffness and hypertension in mice models. Also, promoted the expression of AMPKα, eNOS, and SIRT1

[67]

 Hypertension

3

BM-MSCs

MSC transplantation improved collagen deposition and attenuated EndMT and factor-2α

[68]

4

Skin-Derived MSCs

Decreased vascular damage and systolic blood pressure. Reduced Th17 cells in peripheral blood in a mouse model

[69]

5

UC-MSCs

Exosomes lessened hypertrophy in the right ventricle and caused pulmonary vascular remodeling in a rat model

[70]

1

Ad-MSCs

Exosomes suppressed cardiac dysfunction and apoptosis, and increases in M2 polarization was observed

[71]

2

BM-MSCs

Improved angiogenesis and cell survival in mouse model

[72]

 Myocardial Infarction

3

Unknown source MSCs

Exosomes from SDF1 overexpressing MSCs increased microvascular restoration in endothelial cells and inhibited apoptosis of myocardial cells

[73]

4

BM-MSCs

Anti-mR-155-5p MScs improved angiogenesis and cell survival even compared to control MSCs and no MSCs in the mouse model

[72]

5

UC-MSCs

Exosomes from TIMP2 overexpressed MSCs promoted angiogenesis at the infarction site in a rat model

[74]

1

BM-MSCs

Injection of exosomes from MSCs improved neurogenesis and angiogenesis in mouse models. Reduction of IL-1β expression was also observed

[75]

2

UC-MSCs

Exosomes reduced inflammation in vitro and lowered infarct volume. Enhanced activation of microglia

[76]

 Stroke

3

Various sources MSCs

MSCs as adjuvant therapy improved motor functions in to lower extremities in middle cerebral artery infarction sites

[77]

4

BM-MSCs

MSCs’ extracellular vesicles promoted angiogenesis and neurogenesis in the stroke model

[78]

5

BM-MSCs

Exosomes improved neurological function and enhanced neuroprotective effects in type 2 diabetic rat stroke model

[79]

1

UC-MSCs

Administration of MSCs increased expression of hepatocyte growth factor

[80]

2

Unknown source MSCs

MSCs overexpressing adrenomedullin enhanced heart function and increased cell survival in rat model

[81]

 Heart Failure

3

Human Amniotic MSCs

Nanoparticle labeled MSCs increased cell homing and enhanced myocardial hypertrophy and heart function in a rat model

[82]

4

Ad-MSCs

Enhancing AD-MSC exosomes through adiponectin treatment improved cardiac function and reduced inflammation and fibrosis in a mouse model

[83]

5

BM-MSCs

Injection of BM-MSCs reduced myocardial infarction size and interstitial fibrosis thus enhancing heart rate variability

[84]

1

UC-MSCs

MSCs lowered the percentage of infarct size change

[85]

2

BM-MSCs and UC-MSCs

Transplantation of MSCs along with Coronary Arter Bypass Grafting Surgery showed decline in NT-proBNP

[86]

 Chronic Ischemic Cardiomyopathy

3

BM-MSCs

MSC infusion significantly increases and improves cardiac function

[87]

4

BM-MSCs and UC-MSCs

Intramyocardial injection of MSCs improved left ventricle function in 1, 3, 6 and 12 month followups

[88]

5

BM-MSCs

Intramyocardial injection of MSCs significantly improved regional function of left ventricle in 3 and 6 months

[89]

Immune-related diseases

Study Number

Type of MSC used in study

Main Effect

References

1

BM-MSC

Decreased blood glucose. Increased C-peptide and insulin

[90]

2

UC-MSC

TGFBI is crucial for MSCs to suppress T-cell proliferation

[91]

 Type 1 Diabetes Mellitus

3

BM-MSC

Increase in Langerhans islets diameter and amount of zymogen granules

[92]

4

Ad-MSCs

Maintenance of viability and insulin secretion of pancreatis islets

[93]

5

UC-MSC

Tissue repair of damaged islets. Decrease in blood glucose levels and lesions in renal tissue

[94]

1

UC-MSC

Decrease in blood globulin and platelet level. Decrease in erythrocyte sedimentation rate, C-reactive protein level, and rheumatoid factor

[95]

2

UC-MSC

Decrease in Desease Activity Score-28. Decrease in IL-6 and increase in IL-10. A higher Treg to Th17 ratio

[96]

 Rheumatoid Arthritis

3

UCB-MSC

Decrease in IL-8, IL-6, IL-1β, and TNF-α

[97]

4

BM-MSC

Decrease microRNA-584e. Reduction in NF-κB activity

[98]

5

BM-MSC

Greater improvements in knee injury

[99]

1

UC-MSC

Decrease in SLE Disease Activity Index. Improvements in levels of serum albumin

[100]

2

BM-MSC

Increase in CD4 + Foxp3 + regulatory T-cell percentage. Improvement in Glomerular filtration rate, SLE Disease Activity Index, and serological tests

[101]

 Systematic Lupus Erythematosus

3

UC-MSC

Increase in regulatory T-cells. Balance Th1 and Th2 cytokines

[102]

4

UC-MSC

Increase in IFN-γ levels and a decrease in IL-6 levels

[103]

5

UC-MSC

Downregulate inflammatory genes while upregulating miR-181a

[104]

1

BM-MSC

Remission of GVHD

[105]

2

BM-MSC

Decrease in number of Th1 cells

[106]

 Graft vs. Host Disease

3

UC-MSC

Cured cGVHD. Increase in CD4 + CD25 + CD127 − regulatory T cells. Decrease in non-killer cells

[107]

4

BM-MSC

Increase in overall survival time

[108]

5

BM-MSC

Increase in regulatory T-cells and B cells

[109]