Tissue‐engineered islet‐like cell clusters generated from adipose tissue‐derived stem cells on three‐dimensional electrospun scaffolds can reverse diabetes in an experimental rat model and the role of porosity of scaffolds on cluster differentiation

Abstract

In the current study, three-dimensional (3D) nanofibrous scaffolds with pore sizes in the range of 24-250 μm and 24-190 μm were fabricated via a two-step electrospinning method to overcome the limitation of obtaining three-dimensionality with large pore sizes for islet culture using conventional electrospinning. The scaffolds supported the growth and differentiation of adipose-derived mesenchymal stem cells to islet-like clusters (ILCs). The pore size of the scaffolds was found to influence the cluster size, viability and insulin release of the differentiated islets. Hence, islet clusters of the desired size could be developed for transplantation to overcome the loss of bigger islets due to hypoxia which adversely impacts the outcome of transplantation. The tissue-engineered constructs with ILC diameter of 50 μm reduced glycemic value within 3-4 weeks after implantation in the omental pouch of diabetic rats. Detection of insulin in the serum of implanted rats demonstrates that the tissue-engineered construct is efficient to control hyperglycemia. Our findings prove that the 3D architecture and pore size of scaffolds regulates the morphology and size of islets during differentiation which is critical in the survival and function of ILCs in vitro and in vivo. K E Y W O R D Sdiabetes, electrospun three-dimensional scaffolds, in vivo, islet tissue engineering, stem cells

White Adipose Tissue as a Site for Islet Transplantation

“…These functions of ADMSCs are characterized as supportive effects for promoting the engraftment of transplanted islets. On the other hand, transplanted ADMSCs can ameliorate the diabetic condition by enhancing the proliferation of transplanted islet cells [98], by differentiation into insulin-producing cells themselves [99,100], and by promoting insulin-releasing function of cotransplanted islets [91,93].…”

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

“…When human MSC (hMSC) were inoculated in 3D ECM-like fibrous structures, the smaller pore size exhibited higher overall stiffness and significantly enhanced hMSC collagen and mineral deposition, enhancing osteogenesis [ 32 ]. A 3D electrospun nanofibre scaffold with a large pore size supported the differentiation of rat adipose MSCs (rAMSCs) into islet-like clusters [ 33 ]. The addition of different copolymers to PCL produced micron fibres with a porous topology that allowed cultured rat neural stem progenitor cell (NSPC) to differentiate into astrocytes and neurons in the absence of any growth factors, demonstrating the role of the porous topology of the fibres [ 34 ].…”

“…Tissue engineering of stem cells derived from adipose tissue can reduce hyperglycaemia and extend lifespan. There is also an opportunity for tissue-engineered islets in future stem cell therapy [ 33 ].…”

Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity

“…Moreover, the embedding hydrogel made neurites extend along and above the scaffolds in multiple layers, compared to scaffolds alone [ 154 , 155 ]. Another example reported the electrospinning of a polyaniline-gelatin-polycaprolactone (PANi-GEL-PCL) nanoscaffold superficially modified by plasma method for bone tissue engineering [ 157 ], but also for bone regeneration [ 158 ], cardiac repair and diabetes [ 159 , 160 ] and aneurysm modeling [ 161 ].…”