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[B. Cell Biology/Stem Cell] B-41

Development of efficient immunomodulatory therapeutics

using microsphere-incorporated secretory factors derived

from canine stem cells

Su-Jeong Oh¹,²,³, Ji-Su Ahn¹,²,³, Ye Young Shin¹,²,³, Min-Hye Song¹, Min-Jung Kang¹, YooJin Seo¹, Jee-

Heon Jeong⁴*, Hyung-Sik Kim¹,²,³*

¹Department of Oral Biochemistry; Dental and Life Science Institute, School of Dentistry, Pusan National University,

Yangsan 50612, Korea, ²Department of Life Science in Dentistry, School of Dentistry, Pusan National University,
Yangsan 50612, Korea, ³Education and Research Team for Life Science on Dentistry, Pusan National University,

Yangsan 50612, Korea, ⁴College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea

Atopic dermatitis (AD), which is one of the most common diseases in dogs, causes economic burden and mental
fatigue to owners because continuous treatments are required due to chronic hypersensitive reactions of the

immune system. In this study, we aimed to develop novel technologies to enhance the immunoregulatory efficacy
of mesenchymal stem cells (MSCs) derived from canine adipose tissue. Three-dimensional 3D spheroids were

generated to enrich the production of immunomodulatory paracrine factors from MSCs. Among previously reported
soluble factors, the expressions of LIF, TSG6, and PGE2 were increased in 3D spheroids compared to conventional

two-dimensionally cultured cells. Next, chitosan-based microspheres containing 3D spheroid-derived secretome
were generated to improve the efficiency of secretome delivery, followed by the injection into murine atopic

dermatitis model. We found that the clinical severity was significantly reduced in the microsphere-treated group
compared to the vehicle-treated group. Moreover, epidermal thickness and immune cell infiltration in the lesion

were significantly decreased in the microsphere-injected group. Taken together, in the present study, we suggest
novel convergent technologies to enhance the immune regulatory functions of MSCs for the treatment of canine

atopic dermatitis.