# SSEA3 and CD105 positivity are associated with the treatment potency of human neural crest-derived nasal turbinate stem cells for Alzheimer’s disease

**Authors:** Jung Yeon Lim, Jung Eun Lee, Minho Lee, Haewon Shim, Sang In Park, Soon A. Park, Sin-Soo Jeun, Sheng-Min Wang, Sunghwan Kim, Seung Ho Yang, Hyun Kook Lim, Sung Won Kim

PMC · DOI: 10.1186/s40035-026-00539-3 · Translational Neurodegeneration · 2026-03-03

## TL;DR

This study shows that nasal turbinate stem cells with higher levels of SSEA3 and CD105 markers are more effective in treating Alzheimer’s disease in mice and human brain models.

## Contribution

The study identifies SSEA3 and CD105 as potential markers for predicting the therapeutic efficacy of nasal turbinate stem cells in Alzheimer’s disease.

## Key findings

- NTSCs with higher SSEA3+/CD105+ cell percentages showed better in vitro properties and improved cognitive function in AD models.
- Both high SSEA3+/CD105+ NTSCs and isolated SSEA3+/CD105+ cells reduced AD-related pathology in mice and cerebral organoids.
- No significant difference was found between high SSEA3+/CD105+ NTSCs and isolated SSEA3+/CD105+ cells in treating AD pathology.

## Abstract

Stem cells have the potential to treat Alzheimer’s disease (AD), but clinical outcomes are unpredictable due to inter-donor differences in stem cell properties. This study aimed to determine whether the pluripotency marker SSEA3 and the mesenchymal marker CD105 positivity are associated with the therapeutic efficacy of human neural crest-derived nasal turbinate stem cells (NTSCs) for AD.

The therapeutic effects of NTSCs obtained from different donors, with varying percentages of SSEA3+/CD105+ cells, were explored in 5 × FAD transgenic AD mice and cerebral organoids derived from induced pluripotent stem cells (iPSC) of three AD patients. Neuropathological changes associated with AD were examined, including expression of beta-amyloid, inflammation, and neuronal survival. Cognitive functions were evaluated by the Morris water maze (MWM) test.

NTSCs from different donors improved cognitive function and AD-related neuropathology to varying degrees, depending on the percentage of SSEA3+/CD105+ cells. Compared with NTSCs with a lower percentage of SSEA3+/CD105+ cells (NTSCs-L), NTSCs with a higher percentage of SSEA3+/CD105+ cells (NTSCs-H) showed greater properties in vitro, including proliferative capacity, multilineage differentiation potency, and secretion of neuroprotective cytokines. These properties were comparable to those of pure SSEA3+/CD105+ cells isolated from NTSCs (NTSCs-SC). Both NTSCs-H and NTSCs-SC improved cognitive function and reduced cerebral Aβ deposition, inflammation, and neuronal death in AD model mice. Furthermore, NTSCs-H and NTSCs-SC decreased Aβ aggregates, tau hyperphosphorylation, neuronal death, microglial numbers, and inflammatory cytokine levels in AD cerebral organoids. However, there was no significant difference in AD-related pathological changes between NTSCs-H and NTSCs-SC treatment groups.

Our findings suggest that SSEA3/CD105 positivity is a potential marker of NTSC therapeutic efficacy for the treatment of AD. Future studies should focus on enhancing the therapeutic potential of SSEA3+/CD105+ NTSCs by improving their functional efficacy and consistency, and advancing their use in clinical settings.

The online version contains supplementary material available at 10.1186/s40035-026-00539-3.

## Linked entities

- **Proteins:** Eng (endoglin), MAPT (microtubule associated protein tau)
- **Diseases:** Alzheimer’s disease (MONDO:0004975)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Eng (endoglin) [NCBI Gene 13805] {aka CD105, Endo, S-endoglin}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Vcam1 (vascular cell adhesion molecule 1) [NCBI Gene 22329] {aka CD106, Vcam-1}, Dlg4 (discs large MAGUK scaffold protein 4) [NCBI Gene 13385] {aka Dlgh4, PSD-95, PSD95, SAP90, SAP90A}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, TIMP2 (TIMP metallopeptidase inhibitor 2) [NCBI Gene 7077] {aka CSC-21K, DDC8}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Timp2 (tissue inhibitor of metalloproteinase 2) [NCBI Gene 21858] {aka D11Bwg1104e, Timp-2}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, AIF1 (allograft inflammatory factor 1) [NCBI Gene 199] {aka AIF-1, IBA1, IRT-1, IRT1}, alp (alopecia, recessive) [NCBI Gene 11691], MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Nfkbia (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) [NCBI Gene 18035] {aka Nfkbi}, Nes (nestin) [NCBI Gene 18008] {aka ESTM46, Ifaprc2, Marc2, RC2}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, S100b (S100 protein, beta polypeptide, neural) [NCBI Gene 20203] {aka Bpb}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Iba1 (induction of brown adipocytes 1) [NCBI Gene 114737], Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, ANG (angiogenin) [NCBI Gene 283] {aka ALS9, HEL168, RAA1, RNASE4, RNASE5}, Mme (membrane metallo endopeptidase) [NCBI Gene 17380] {aka 6030454K05Rik, CALLA, CD10, NEP, SFE}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, MRAP (melanocortin 2 receptor accessory protein) [NCBI Gene 56246] {aka B27, C21orf61, FALP, GCCD2, MRAP1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, Rbfox3 (RNA binding protein, fox-1 homolog (C. elegans) 3) [NCBI Gene 52897] {aka Fox-3, Hrnbp3, NeuN, Neuna60}, Tspo (translocator protein) [NCBI Gene 12257] {aka Bzrp, IBP, PBR, Tspo1}, Nlrp1a (NLR family, pyrin domain containing 1A) [NCBI Gene 195046] {aka CARD7, DEFCAP, Gm14, Gm15, NAC, Nalp1}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, Hes1 (hes family bHLH transcription factor 1) [NCBI Gene 15205] {aka Hry, bHLHb39}, Hes5 (hes family bHLH transcription factor 5) [NCBI Gene 15208] {aka bHLHb38}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, Cd1d1 (CD1d1 antigen) [NCBI Gene 12479] {aka CD1.1, Cd1a, Cd1d, Ly-38}, Spp1 (secreted phosphoprotein 1) [NCBI Gene 20750] {aka 2AR, Apl-1, BNSP, BSPI, Bsp, ETA-1}, TSPO (translocator protein) [NCBI Gene 706] {aka BPBS, BZRP, DBI, IBP, MBR, PBR}, Fabp7 (fatty acid binding protein 7, brain) [NCBI Gene 12140] {aka B-FABP, BFABP, Blbp, MRG}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076] {aka CLGI, EPA, EPO, HCI, TIMP, TIMP-1}
- **Diseases:** NTSCs (MESH:D054391), stroke (MESH:D020521), neurological disease (MESH:D020271), pain (MESH:D010146), mitochondrial dysfunction (MESH:D028361), Parkinson's disease (MESH:D010300), inflammation (MESH:D007249), neurodegenerative diseases (MESH:D019636), neuroinflammation (MESH:D000090862), neurotoxic (MESH:D020258), AD (MESH:D000544), tumor (MESH:D009369), Dementia (MESH:D003704), amyloid (MESH:C000718787), neuronal death (MESH:D009410), cognitive decline (MESH:D003072), neuropathological (MESH:D009422), nasal obstructions (MESH:D015508), death (MESH:D003643), tumorigenic (MESH:D002471), ALS (MESH:D000690), Astrogliosis (MESH:D005911), toxicity (MESH:D064420), infection (MESH:D007239), MI (MESH:D009203), turbinate hypertrophy (MESH:D006984)
- **Chemicals:** oil red O (MESH:C011049), water (MESH:D014867), GlutaMAX (MESH:C054122), Fluo-4 (MESH:C409648), biotin (MESH:D001710), gentamicin (MESH:D005839), formic acid (MESH:C030544), paraffin (MESH:D010232), OCT (MESH:C051883), saline (MESH:D012965), streptomycin (MESH:D013307), Bis-Tris (MESH:C026272), polysaccharide (MESH:D011134), FITC (MESH:D016650), N2 (MESH:D009584), EDTA (MESH:D004492), xylazine (MESH:D014991), PFA (MESH:C003043), Zoletil (MESH:C006131), ketoprofen (MESH:D007660), CO2 (MESH:D002245), DMSO (MESH:D004121), DAPI (MESH:C007293), GLU (MESH:D005947), CRE (MESH:D003404), formalin (MESH:D005557), Calcium (MESH:D002118), alizarin red S (MESH:C004468), Alexa Fluor 546 (MESH:C481052), PBS (MESH:D007854), heparin (MESH:D006493), PVDF (MESH:C024865), Pluronic F-127 (MESH:D020442), Hematoxylin (MESH:D006416), penicillin (MESH:D010406), 6E10 (-), H&amp;E (MESH:D006371), Y27632 (MESH:C108830), FAD (MESH:D005182), 2-mercaptoethanol (MESH:D008623), Alexa Fluor 488 (MESH:C000711379), amino acids (MESH:D000596)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Mutations:** V717I, L286V, I716V, K670N, M671L
- **Cell lines:** HuNu — Mus musculus (Mouse), Hybridoma (CVCL_C7I9)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12955099