Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models

A Biofabrication Strategy for a Custom-Shaped, Non-Synthetic Bone Graft Precursor with a Prevascularized Tissue Shell

“…Distinct from single cell approaches, isolated microvessel fragments retain a native microvessel structure with an endothelial cell lining comprising a patent lumen and surrounded by a mix of perivascular cells, including those associated with the perivascular niche ( Hoying et al, 1996 ; Nunes et al, 2010b ; Nunes et al, 2011 ). In 3D collagen culture, isolated microvessels generate an expanded neovascular network, via sprouting angiogenesis, that inosculates and matures into a stable microcirculation when implanted ( Shepherd et al, 2004 ; Hiscox et al, 2008 ; Nunes et al, 2010a ; Sun et al, 2020 ; Aghazadeh et al, 2021 ). In the graft precursors, neovessels filled the outer tissue space via angiogenesis from the isolated “parent” microvessels while the MSCs compacted the tissue space during the 3 weeks of in vitro culturing.…”

Emerging diabetes therapies: Bringing back the β-cells

“…hPSCs also afford us the opportunity to generate other functional cell types to co-culture with sBCs, such as endothelial cells, thereby approximating the native tissue composition more closely. Indeed, recreating an appropriate niche for sBCs can improve their function and engraftment [ 27 ]. Further development of multi cell type hESC/iPSC platforms will enable disease modeling in an isogenic manner, a critical, yet largely unmet need in the wider T1D research space.…”

Pancreatic islets in bed with microvasculature—companions for life

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In Cell Stem Cell, Aghazadeh et al 1 show that human embryonic stem cell-derived pancreatic progenitors can reverse hyperglycemia for several weeks in streptozotocin-induced diabetic mice when co-transplanted with microvessel fragments into the subcutaneous space.

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“…Taking into consideration the role of vasculature in instructing islet development 7 and supporting mature islet function, 8 Aghazadeh et al 1 show that the subcutaneous site can be rendered hospitable for transplanted islets through incorporation of adipose-derived microvessels-small vascular fragments which can be purified after partial digestion and sieving of adipose tissue. Microvessel fragments retain most of the architecture, cell-cell contacts, and extracellular matrix components of native microvessels, which accelerates the formation of functional interconnected networks after transplantation.…”

“…Challenges aside, the work presented by Aghazadeh et al 1 highlights the importance of creating a welcoming vascular bed to reduce early graft losses and sustain long-term function of transplanted cells or reconstructed tissues. One hundred years after the discovery of insulin, a durable, effective cell-based therapy for diabetes appears in reach.…”