Therapeutic potential of mesenchymal stem cells for refractory inflammatory and immune skin diseases

Figures & data

Figure 1. MSC therapy could rebalance the amount and function of immune cells and suppress inflammatory mediators in psoriasis model.

Table 1. Clinical trials of MSC therapy in psoriasis.

ClinicalTrials.gov Identifier	Locations	Phase	Estimated Enrollment	Age	Route of delivery	Dose	Frequency	Follow up	Type of MSC	Primary outcome	Secondary outcome
NCT03765957	Xiangya Hospital, Central South University, China	Early Phase 1	12 participants	18–65 years (Adult, Older Adult)	Intravenous infusion.	(1.5–2) *10^6 cells/kg or (2.5–3) *10^6 cells/kg	4 times (week 0,2,4,6)	6 months	Human Umbilical Cord-derived Mesenchymal Stem Cells	PASI75 and PGA at month6	DLQI and AE at baseline and month6
NCT03745417	Guangdong Provincial Hospital of Traditional Chinese Medicine, China	Phase 1, 2	5 participants	18–65 years (Adult, Older Adult)	Intravenous infusion.	2 × 10^6 cells/kg	5 times (week 0,2,4,6,8).	12 weeks	Human Umbilical Cord-derivedMesenchymal Stem Cells	PASI score at 12 weeks (plus or minus 3 days)	PASI score, relapse rate, Pruritus scores, BSA%, DLQI at 12 weeks (plus or minus 3 days)
NCT04785027	Guangdong Provincial Hospital of Traditional Chinese Medicine, China	Phase 1, 2	16 participants	18–65 years (Adult, Older Adult)	Intravenous infusion.	2 × 10^6 cells/kg	5 times (week 0,2,4,6,8).	12 weeks	Allogeneic Adipose-derived Mesenchymal Stem Cells	PASI score at 12 weeks (plus or minus 3 days)	PASI score, relapse rate, Pruritus scores, BSA%, DLQI at 12 weeks (plus or minus 3 days)
NCT03392311	Guangdong Provincial Hospital of Traditional Chinese Medicine, China	Phase 1, 2	8 participants	18–65 years (Adult, Older Adult)	Intravenous infusion	2 × 10^6 cells/kg	5 times (week 0,2,4,6,8).	12 weeks	Adipose-derived multipotent mesenchymal stem cells	PASI score at 12 weeks (plus or minus 3 days)	PASI score, relapse rate, Pruritus scores, BSA%, DLQI at 12 weeks (plus or minus 3 days)
NCT04275024	Guangdong Provincial Hospital of Traditional Chinese Medicine, China	NotApplicable	8 participants	18–65 years (Adult, Older Adult)	Intravenous infusion	2 × 10^6 cells/kg	5 times (week 0,2,4,6,8).	12 weeks	Adiposederived multipotent mesenchymal stem cells	PASI score at 12 weeks (plus or minus 3 days)	PASI score, relapse rate, Pruritus scores, BSA%, DLQI at 12 weeks (plus or minus 3 days)
NCT03265613	Guangdong Provincial Hospital of Traditional Chinese Medicine, China	Phase 1, 2	7 participants	18–65 years (Adult, Older Adult)	Intravenous infusion.	0.5 × 10^6 cells/kg	3 times (week 0,4,8).	12 weeks	Adipose-derived multipotent mesenchymal stem cells	AE, SAE at 12 weeks (plus or minus 3 days)	PASI score, Pruritus scores, BSA%, DLQI at 12 weeks (plus or minus 3 days)
NCT02491658	Affiliated Hospital to Academy of Military Medical Sciences, China	Phase 1, 2	30 participants	18–65 years (Adult, Older Adult)	Unclear	1.0 × 10^6 cells/kg	6 times (week 0,1,2,3,5,7)	1 year	Human Umbilical Cord-derived Mesenchymal Stem Cells	PASI score and DLQI at baseline and 8 weeks	Body temperature, blood pressure up to 3 months. PASI score and DLQI at month 6,9,12
NCT03424629	Peking University Third Hospital and Tianjin Ever Union Biotechnology Co., Ltd., China	Phase 1	57 participants	18–60 years (Adult)	Intravenous infusion.	1.0 or 3.0 × 10^6 cells/kg	6 times (week 0,1,2,3,5,7)	52 weeks	Human Umbilical Cord-derived Mesenchymal Stem Cells	PASI75 and PGA at week 6	PASI90 at week20.PASI75 and PGA at week 12,16,36,52.AE and SAEs form week 0 to 52. Relapse from week 8 to 52.
NCT02918123	The Catholic Univ. Korea Seoul, St. Marry’s Hospital, Korea	Phase 1	9 participants	19–65 years (Adult, Older Adult)	Subcutaneous injection	0.1 or 0.5 or 2.0 × 10^8 cells	Once	4 weeks	Human Umbilical Cord-derived Mesenchymal Stem Cells	AE, safety lab tests, physical examination, ECG, vital signs, variation of Cytokine, PASI, BSA at 4 weeks follow up	Not applicable
NCT05523011	National University Hospital, Singapore	Phase 1	10 participants	21 years and older (Adult, Older Adult)	Topical	100 µg	Three doses per day, 20 days	20 days	MSC Exosome ointment	TEAEs, Vital signs and blood test, Visual assessments of the area of application based on SCORAD	Not applicable

PASI 75, Psoriasis Area and Severity Index ≥75%.

PGA, Physician Global Assessment.

DLQI, Dermatology Life Quality Index.

AE, Adverse event.

SAE, Serious adverse event.

ECG, Electrocardiograph.

BSA%, the Body Surface Area.

SCORAD, SCORing Atopic Dermatitis.

TEAEs, Treatment-emergent adverse events.

Table 2. Clinical trials of MSC therapy in systemic sclerosis.

ClinicalTrials.gov Identifier	Location	Phase	Estimated Enrollment	Age	Route of delivery	Dose	Frequency	Follow up	Type of MSC	Primary outcome	Secondary outcome
NCT05016804	Medical Surgical Associates Center,	Phase 1	20 participants	Child, Adult, Older Adult	Intravenous Infusion	1.0 × 10^6 cells	once	4 years	Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell	adverse events	skin score and FVC
NCT00962923	the Affiliated Drum Tower Hospital of Nanjing University Medical School, China	Phase 1, 2	20 participants	15–65 years (Child, Adult, Older Adult)	Intravenous infusion	1.0 × 10^6cells/kg	Once	Unclear	Allogeneic mesenchymal stem cells	mRSS score, HRQOL score, SF-36 score	Remission for organ function, DLCO, PAP, blood test, SSc Serology, Change of peripheral blood B and T cells
NCT04432545	Universidad de la Sabana， Colombia	Not applicable	Not applicable	18–65 years (Adult, Older Adult)	Intravenous infusion	2.0 × 10^6 cells/kg	ten days after each application of thecyclophosphamide schedule	6 months	Allogeneic mesenchymal stem cells from Wharton ́s jelly	Unclear	Unclear
NCT02213705	Saint-Louis Hospital, France	Phase 1, 2	20 participants	18–70 years (Adult, Older Adult)	Unclear	Unclear	Unclear	2 years	allogeneic mesenchymal stem cells	Toxicity (2 years)	Survival, progression free survival, Rodnan score (2 years), Clinical response (3, 6, 9, 12 months)
NCT02975960	Seoul St. Mary’s hospital, Korea	Not Applicable	7 participants	18 years and older (Adult, Older Adult)	Unclear	Unclear	Unclear	12 weeks	Adipose Tissue-derived Mesenchymal Stem Cells	mRSS of hands	Raynaud’s condition score, Visual Analog Score, Kapandji score, Cochin hand function scale, Systemic sclerosis HAQ, peripheral vasculature, finger circumference
NCT03211793	Universitair Medisch Centrum Utrecht, Netherlands	Phase 1, 2	20 participants	18 years and older (Adult, Older Adult)	Intramuscular injection	5.0 × 10^7 cells	8 intramuscular injections at designated sites	52 weeks	Allogeneic bone marrow derived mesenchymal stem cells	Toxicity of thetreatment	SAE, Numerical Rating Scale, digital ulcer visual analogue scale, perceived pain based on the use of analgesics, SF-36, HAQ-DI, Hand function, EQ-5D-5 L .,etc
NCT01745783	University Hospital Reina Sofia, University Regional Hospital Carlos Haya, University Hospital Virgen Macarena, Spain	Phase 1, 2	26 participants	18–50 years (Adult)	Intravenous infusion	1-2 × 10^6 cells/kg	once	12 months	Autologous bone marrow derived mesenchymal stem cells	SAE	Disease activity on magnetic resonance, EDSS, MSFC, life quality, outbreaks, disease-free patients

mRSS, modified Rodnan Skin Score.

FVC, Forced Vital Capacity.

HSCT, Hematopoietic Stem Cell Transplant.

SAEs, serious adverse reactions.

HRQOL, health-related quality of life.

SF-36, Short-Form 36.

DLCO, diffusion capacity for carbon monoxide.

EDSS, Expanded Disability Status Scale.

MSFC, Changes Multiple Sclerosis Functional Composite.

PAP, pulmonary artery pressure.

HAQ-DI, Health Assessment Questionnaire-Disability Index.

EQ-5D-5 L, EuroQol-5-Domain-5-Level health questionnaire.

Table 3. Clinical trials of MSC therapy in dermatomyositis.

ClinicalTrials.gov Identifier	Location	Phase	Estimated Enrollment	Age	Route of delivery	Dose	Frequency	Follow up	Type of MSC	Primary outcome	Secondary outcome
NCT04723303	University of Florida, USA	Early Phase 1	22participants	18–90 years (Adult, Older Adult)	Intravenous infusion	0.5 or 1.0 or 2.0 × 10^8 cells	Unclear	Unclear	Umbilical Cord Lining Stem Cells	DLT(within24 hours)	Not applicable
NCT04976140	Seoul National University College of Medicine, Soonchunhyang University Seoul Hospital, Hanyang University Seoul Hospital, Korea	Phase 1， 2	18 participants	19 years and older (Adult, Older Adult)	Intravenous infusion	Unclear	Unclear	12 weeks	Human umbilical cord mesenchymal stem cell (UC-MSC) derived allogeneic mitochondria	DLT, IMACS-TIS	IMACS-TIS, response rate of IMACS-TIS, CSAM, CDASI and PPNRS

DLT: Dose Limiting Toxicity.

PBSC: peripheral blood stem cell.

IMACS-TIS: international Myositis And Clinical Studies group-Total Improvement Score.

CSAM: Core Set Activity Measures.

CDASI: Cutaneous Dermatomyositis Disease Area and Severity Index.

PPNRS: Peak Pruritus Numeral Rating Scale.

Figure 2. The anti-inflammatory effect and immune modulation of MSC or its cell-free products in atopic dermatitis model.

Table 4. Clinical trials of MSC therapy in atopic dermatitis.

ClinicalTrials.gov Identifier	Location	Phase	Estimated Enrollment	Age	Route of delivery	Dose	Frequency	Follow up	Type of MSC	Primary outcome	Secondary outcome
NCT02888704	Chungnam National University Hospital，Korea	Phase 1	13participants	19–70 years (Adult, Older Adult)	Intravenous infusion	1.0 or3.0 × 10^8 cells	Once	12 weeks	Adult humanmesenchymal stem cells	AE (12 weeks follow-up after treatment)	SCORAD, IGA, EASI, Serum IgE, PGE2, ECP, CCL17, CCL27
NCT03252340	Chungnam National University Hospital，Korea	Phase 1	11 participants	19–70 years (Adult, Older Adult)	Intravenous infusion	1.0 or 3.0 × 10^8 cells	Once	60 months	Adult human mesenchymal stem cells	Tumor formation (60 months)	AEs (60 months)
NCT01927705	Catholic Medical Center, Korea	Phase 1, 2	34participants	20–60 years Adult	Unclear	2.5or5.0 × 10^7 cells	once	4 weeks	Human Umbilical Cord Blood derived-Universal Stem Cells	SCORAD Index (4 weeks follow-up after treatment)	SCORAD total score and index, the degree of disease, IGA, EASI, Serum IgE (4 weeks follow-up after treatment)
NCT03458624	Seoul ST. Mary’s Hospital, Korea	Phase 1	14 participants	19–70 years (Adult, Older Adult)	Intravenous infusion	Unclear	Unclear	3 years	Unclear	AE (3 years)	SCORAD, IGA, EASI, Serum IgE (3 years)
NCT05004324	Chosun University Hospital, Korea	Phase 3	308 participants	19 years and older (Adult, Older Adult)	Unclear	5.0 × 10^7 cells/1.5 ml	Once with five regions (both upper arms, both thighs, and abdomen)	12 weeks	Human Umbilical Cord Blood derived-Universal Stem Cells	EASI	EASI, IGA, SCORAD, BSA, NRS, POEM, DLQI, Resuce medicine (week 2,4,8,12,24)
NCT03269773	Pusan National University Hospital, Chonnam National University Hospital, Dongguk University Medical Center, Gachon University Gil Medical Center, Catholic Medical Center, Asan Medical Center, Chung-Ang University Healthcare System, Hanyang University Medical Center, Samsung Medical Center, Seoul National University Hospital, Ajou University Hospital	Phase 3	197 participants	19 years and older (Adult, Older Adult)	Unclear	5.0 × 10^7 cells/1.5 ml		24 weeks	Human Umbilical Cord Blood derived-Universal Stem Cells	EASI50	EASI, IGA, SCORAD, BSA, IgE, TNF-a, IL-4, IL-5, IL-6, IL-8, IL-13, IL-31, TARC (CCL17) and CCL 27, Total number of use and consumed amount of rescue medicine (week12,24)
NCT04179760	Inha University Hospital, Korea	Phase 1, 2	92 participants	19 years and older (Adult, Older Adult)	Intravenous infusion	1.0 × 10^6 cells/kg	3 times (week 0,2,4)	24 weeks	Allogeneic human bone marrow-derived mesenchymal stem cells	EASI50	EASI, IGA, NRS, BSA, SCORAD, DLQI, POEM, IgE, eosinophil count, IL13, IL17, TRAC, IL22 (week 4, 8, 12, 16, 20, 24)
NCT04137562	Chungnam National University Hospital, Korea University AnSan Hospital, Chung-Ang University Hospital, Kyunghee University Medical Center, Seoul National University Hospital, SMG-SNU Boramae Medical Center	Phase 2	118 participants	19–70 years (Adult, Older Adult)	Intravenous infusion	0.5 × 10^8 cells/5 mL	Twice	5 years	Adult human mesenchymal stem cells	EASI50 (week16)	EASI, SCORAD, Severity, IGA, IGEPGE2, ECP, immune cytokine, Remedy used days, frequency and subjects (week 4,8,12,16).

SCORAD, SCORing Atopic Dermatitis.

IGA, Investigator’s global assessment.

EASI, eczema area and severity index.

AE, Adverse event.

IgE, Immunoglobulin E.

PGE2, prostaglandin E2.

ECP, eosinophil cationic protein.

CCL17, Chemokine ligand 17.

CCL27, Chemokine ligand 27.

NRS, Numerical Rating Scale.

POEM, Patient-Oriented Eczema Measure.

DLQI, Dermatology Life Quality Index.

BSA, Body Surface Area.