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Alginate Encapsulation of 3D Spheroidal Mesenchymal Stem Cell
for Treatment of Inflammatory Bowel Disease

1
Junhyeung Park , Tiep Tien Nguyen , Jee-Heon Jeong *
1
1
1 College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan-si, Gyeongbuk-do 38541, Korea
jeeheon@yu.ac.kr
INTRODUCTION RESULTS
2. Viability of encapsulated ADMSCs spheroids

Viability of ADMSC spheroids before and after encapsulation assessed by
Currently, mesenchymal stem cell (MSC)-based therapy offers a promise for the LIVE/DEAD assay. Non-encapsulated spheroids and encapsulated spheroids were
given conditions. Still, low cell retention and survival rate at the diseased site hinder stained with AO (0.67 μM) and PI (75 μM) (scale bar: 200 μm).
this cellular therapy. Therefore, this study was aimed at developing a robust method
of alginate encapsulation of MSC spheroids, namely “Surface triggering in situ
gelation (STIG), for the treatment of chronic inflammatory bowel disease (IBD). We 3. Relief of DSS-induced murine colitis by encapsulated hADMSC spheroids
hypothesized that alginate-encapsulated MSC spheroids would allow improved cell
retention time and prolong their therapeutic efficacy. A B
METHODOLOGY

1. Preparation of PD-CaMS-microspheres

00
C D
Calcium carbonate microspheres (CaCO 3 -MS) were first prepared by a simple
reaction between calcium chloride (CaCl 2 ) and sodium carbonate (Na 2 CO 3 ). Next,
polydopamine (PD) was coated on the microspheres, via reaction with dopamine
solution, to form cell-adhesive PD-CaCO 3 -MS
2. Surface triggering in situ gelation (STIG) for cell encapsulation

Spheroids were mixed with a suspension of PD-CaCO 3 -MS in a buffer (pH 8.0) for
10 min to allow the formation of “Cell-particle conjugate”. After washings, the
conjugated spheroids were incubated with the solution of alginate and D-(+)-
gluconic acid-δ-lactone (GDL) to allow spontaneous encapsulation of spheroids. Retention of transplanted MSCs measured using qPCR analysis of human specific
The role of GDL was to release Ca 2+ ions from the conjugated particles, which were ALU gene (Fig. A) Average of 30 days disease activity index after administration of
then complexed with alginate DSS, disease activity index was evaluated by the mean score of stool consistency (0-
3), body weight losing (0-3), presence of bleeding on the stool or rectal bleeding (0-4)
3. In vivo experiments (Mean ± SD, n = 6, * represent P < 0.05) (Fig. B) Representative images of
Murine chronic colitis model was induced by repeated oral administration of dextran hematoxylin and eosin (H&E) stained section showing mononuclear immune cells
sodium sulfate (DSS). For the treatment, naked and encapsulated spheroids were infiltration (represented by red *), reduction of goblet cell (represented by yellow #),
injected intraperitoneally (i.p.) to the mice. Disease activity indices (DAI) and and presence of epithelial ulceration or erosion (represented by arrow) (Fig. C). The
histological score were then evaluated. histological scores were measured in view of inflammatory cell infiltration, the
presence of mucosal damage and crypts, and the reduction of goblet cell (n =6. **
RESULTS represent P < 0.01, *** represent P < 0.001) (Fig .D)
1. Characterization of PD-CaMS
CONCLUSION
This study demonstrated a unique encapsulation technique for individual
encapsulation of hADMSC spheroids. Additionally, the result indicated that MSC En
showed long-term therapeutic effect against DSS-induced colitis compared to
MSC 3D . The applications of this novel strategy could potentially be extended in a
variety of fields to provide a precisely-controlled microscale alginate layer on other
biological area.
REFERENCE
Pham et al. Adv. Funct. Mater. 2021, 31, 2010169
Regmi & Jeong. Macromolecular Research. 2016, 24, 1037-1046
The PD-CaCO 3 MS were successfully prepared with the spherical morphology and
average size around 5 μm.