Deconstructed Microfluidic Bone Marrow On‐A‐Chip to Study Normal and Malignant Hemopoietic Cell–Niche Interactions. Issue 43 (29th August 2019)

• Record Type: Journal Article
• Authors: Aleman, Julio; George, Sunil K.; Herberg, Samuel; Devarasetty, Mahesh; Porada, Christopher D.; Skardal, Aleksander; Almeida‐Porada, Graça
• Is Part Of: Small. Volume 15:Issue 43(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-08-29
• Subjects: bone marrow niche -- hematopoietic stem and progenitor cells -- homing -- microfluidics -- tissue chip; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201902971
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Human hematopoietic niches are complex specialized microenvironments that maintain and regulate hematopoietic stem and progenitor cells (HSPC). Thus far, most of the studies performed investigating alterations of HSPC‐niche dynamic interactions are conducted in animal models. Herein, organ microengineering with microfluidics is combined to develop a human bone marrow (BM)‐on‐a‐chip with an integrated recirculating perfusion system that consolidates a variety of important parameters such as 3D architecture, cell–cell/cell–matrix interactions, and circulation, allowing a better mimicry of in vivo conditions. The complex BM environment is deconvoluted to 4 major distinct, but integrated, tissue‐engineered 3D niche constructs housed within a single, closed, recirculating microfluidic device system, and equipped with cell tracking technology. It is shown that this technology successfully enables the identification and quantification of preferential interactions—homing and retention—of circulating normal and malignant HSPC with distinct niches. Abstract : Described is the deconstruction of the bone marrow niche cellularly into four distinct 3D niche types (sinusoidal, arterial, mesenchymal, and osteoblastic) within a microfluidic tissue chip. Shown is 1) preservation of niche‐specific markers, 2) the capability to live‐track healthy and malignant hematopoietic stem progenitor cells (HSPC), and 3) evidence that healthy versus malignant HSPC show different predilection for homing/engrafting.