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Development of efficient immunomodulatory therapeutics

using microsphere-incorporated secretory factors derived

from canine stem cells

1
Su-Jeong Oh 1,2,3 , Ji-Su Ahn 1,2,3 , Ye Young Shin 1,2,3 , Min-Hye Song , Min-Jung Kang , Yoojin Seo ,
1
1

4
Jee-Heon Jeong , and Hyung-Sik Kim 1,2

1 Department of Oral Biochemistry; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Korea

2 Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan 50612, Korea

3 Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, Korea

4 College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Korea

Abstract Results

Atopic dermatitis (AD), which is one of the most 1. Canine MSC isolation and 3D spheroid 5. Evaluation of chitosan microsphere

common diseases in dogs, causes economic generation based on BSA loading

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 2. 3D spheroid characterization

enrich the production of immunomodulatory

paracrine factors from MSCs. Among previously

reported soluble factors, the expressions of LIF,

TSG6, and PGE 2 were increased in 3D

spheroids compared to conventional two- 6. Analysis of 3D spheroid secretome

dimensionally cultured cells. Next, chitosan- loading and release

based microspheres containing 3D spheroid- 3. Analysis of immunoregulatory factors

derived secretome were generated to improve from 3D spheroids

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 7. Efficacy and safety of microsphere-

decreased in the microsphere-injected group. delivered secretome in vivo

Taken together, in the present study, we suggest 20 Df

novel convergent technologies to enhance the 15 #2 CM
#2 MS

immune regulatory functions of MSCs for the Clinical Severity (Time course) 10

treatment of canine atopic dermatitis. 5 *

0 **
Purpose 2wk 3wk 4wk

To enhance the therapeutic efficacy of canine

adipose tissue-derived stem cells for the treatment

of atopic dermatitis by

1. harvesting paracrine factors from 3D

spheroids enriched with immunoregulatory

factors (proven in previous studies)

4. Generation of chitosan microsphere

Stem Cell Research & Therapy, 2019

2. and incorporating secretome from 3D

spheroids using chitosan-based microsphere

for improved delivery Acknowledgement

This study was carried out with the support of

"Cooperative Research Program for Agriculture

Science and Technology Development (Project No.

PJ015596)" Rural Development administration,

Republic of Korea.