Sensitivity study for the key parameters in heterospheroid preparation with insulin-secreting beta-cells and mesenchymal stem cells
Yükleniyor...
Dosyalar
Tarih
2019
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Amer Chemical Soc
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
The outcome of islet transplantation in clinics has been determined by the success of tissue engraftment. The strong immune attack that occurs upon transplantation of beta-cells plays a central role as this attack results in the failure of transplanted tissue. To improve tissue engraftment, deleterious effects of immune reactions should be minimized for Pull function and survival. Here, we report a systematic analysis of the effect of insulin-secreting beta-cell (MIN6) and mesenchymal stem cell (MSC) number and size on the function of beta-cells and present immune protection potential of heterospheroid structures through MSCs and synthetic scaffolds. We prepared 3D heterospheroids with MSCs and MIN6 cells through a hanging-drop approach. To precisely estimate the influence of critical parameters on heterospheroid size and insulin secretion function of beta-cells, we prepared heterospheroids using two independent input variables: (i) initial cell number in each droplet and (ii) MIN6:MSC ratio. We studied the influence of initial cell numbers of 200 and 500, and six different MIN6:MSC ratios (1:0, 0:1, 1:1, 2:1, 5:1, and 10:1) for the preparation of heterospheroids through the hanging drop. Next, we used PEG hydrogels as a semipermeable physical barrier to improve immune protection from cytokines. Through encapsulation of our heterospheroids within PEG hydrogel, we were able to observe sustained beta-cell survival and insulin secretion despite exposure of heterospheroids with proinflammatory cytokines. Insulin secretion was further promoted with glucagon like peptide-1 (GLP-1) incorporation within PEG hydrogel structure. This study is significant to demonstrate the synergistic effects of MIN6-MSC and scaffold-MIN6 interactions and to improve therapeutic efficacy of islet transplantation. Overall, this study comprehensively presents the optimum conditions for the preparation of MIN6-MSC spheroids, utilizes MSCs and GLP-1 functional PEG hydrogels as a scaffold to retain insulin secretion function and further demonstrates protection of heterospheroids exposed to proinflammatory cytokines.
Açıklama
Anahtar Kelimeler
Min6, Msc, Peg Hydrogel, Glp-1, Insulin Secretion, Cytokine Attack, Immune Protection
Kaynak
Acs Biomaterials Science & Engineering
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
5
Sayı
10
Künye
Bal, T., Inceoglu, Y., Karaoz, E., & Kizilel, S. (2019). Sensitivity Study for the Key Parameters in Heterospheroid Preparation with Insulin-Secreting beta-Cells and Mesenchymal Stem Cells. ACS BIOMATERIALS SCIENCE & ENGINEERING, 5(10), 5229–5239. https://doi.org/10.1021/acsbiomaterials.9b00570