Evaluating the efficacy of stem cells in treating severe dry eye disease

Table 1 Diagnostic criteria for primary Sjogren’s syndrome

Diagnostic criteria	Points
Positive anti-SSA antibody from a peripheral blood sample	3
Focal lymphocytic sialadenitis	3
Abnormal ocular staining score 5 out of 7	1
Schirmer test score ≤ 5 mm/5 minutes	1
Unstimulated salivary flow rate ≤ 0.1 mL/minute	1

SSA: Sjogren’s-syndrome-related antigen A.

Table 2 Comparison of different stem cell sources in dry eye disease treatment

Stem cell source	Differentiation potential	Anti-inflammatory properties	Clinical applications	Key findings
AD-MSCs[74,76,84]	Multipotent	High secretion of anti-inflammatory cytokines	Used in limbal stem cell deficiency and corneal wound healing	Show promising anti-inflammatory and regenerative effects
BM-MSCs[36,85,86]	Multipotent	Moderate secretion of anti-inflammatory cytokines	Used in severe DED and Sjögren’s syndrome-related dry eye	Effective in reducing inflammation and promoting epithelial proliferation
UC-MSCs[75,86-90]	Higher plasticity than AD-MSCs and BM-MSCs	High immunomodulatory potential	Investigated for corneal and lacrimal gland regeneration	Exhibits low immunogenicity and enhances corneal healing

AD-MSCs: Adipose-derived mesenchymal stem cells; BM-MSCs: Bone marrow-derived mesenchymal stem cells; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; DED: Dry eye disease.

Table 3 Registered clinical trials for mesenchymal stem cells in dry eye disease from the ClinicalTrials.gov database (July 31, 2024)

No.	Study	Diagnosis	Drug	Intervention	Patient number	Location(s)	Trial reference number (NCT)
1	Effect of UMSCs derived exosomes on dry eye in patients with cGVHD	Dry eye	UMSC-Exo	Transconjunctival injection	27	Guangzhou, Guangdong, China	04213248
2	Mesenchymal stem cell therapy of dry eye disease in patients with Sjögren’s syndrome	Keratoconjunctivitis sicca, in Sjögren’s syndrome	AD-MSCs	Transconjunctival injection	40	Copenhagen, DK, Denmark	04615455
3	Safety and efficacy of pluripotent stem cell-derived mesenchymal stem cell exosome (PSC-MSC-Exo) Eye drops treatment for dry eye disease post refractive surgery and associated with blepharospasm	Dry eye post refractive surgery	PSC-MSC-Exo	Topical eye drops	12	Hangzhou, Zhejiang, China	05738629
4	Treatment with allogeneic adipose-derived mesenchymal stem cells in patients with aqueous deficient dry eye disease	Aqueous deficiency dry eye disease, keratoconjunctivitis sicca	AD-MSCs	Lacrimal gland injection	7	Copenhagen, DK, Denmark	03878628
5	Allogeneic mesenchymal stem cells transplantation for primary Sjögren’s syndrome (pSS)	Keratoconjunctivitis sicca, in Sjögren’s syndrome	AlloMSC	Intravenous infusion (single dose)	20	Nanjing, Jiangsu, China	00953485
6	Therapeutic effect of stem cell eye drops on dry eye disease	Dry eye syndromes	MSC eye drops	Topical eye drops	10	Nanjing, Jiangsu, China	05784519

UMSC-Exo: Umbilical cord-derived mesenchymal stem cell exosome; AD-MSCs: Adipose-derived mesenchymal stem cells; PSC-MSC-Exo: Pluripotent stem cell-derived mesenchymal stem cell exosome; AlloMSC: Allogeneic mesenchymal stem cell; MSC: Mesenchymal stem cell; cGVHD: Chronic graft-vs-host disease; pSS: Primary Sjögren’s syndrome; UMSC: Umbilical cord-derived mesenchymal stem cell.