Table 1.
3D culture systems developed to mimic the bone marrow niche.
| System | Description | Main Results |
|---|---|---|
| Synthetic scaffolds | ||
| Poly (lactic-co-glycolic acid) (PLGA) | PLGA is a biocompatible and biodegradable material. | It does not support CD34+ cells growth [58]. |
| Polycaprolactone (PCL) | elastic mechanical properties and slow degradation rate | Supports CD34+ adhesion and proliferation [58]. |
| Polyurethane (PU) | PU is a polymer with attractive mechanical properties and biocompatible. | Supports Cd34+ proliferation, differentiation and egress [59]. |
| Non-woven polyester fiber/polypropylene mesh | Fibrous material, multiple fibrous layers of polymers. | Supports CD34+ proliferation [60]. |
| Biodegradable zwitterionic hydrogel | Poly-carboxybetaine acrylamide (pCBAA) hydrogel, with zwitterionic segments of 20 alternating K and E residues and a metalloproteinase-cleavable motif for degradation. | Prevents differentiation, maintains self-renewal and reduces metabolic activity of HSCs. Shows superior expansion of primitive HSCs [90]. |
| Bio-functionalized scaffolds | ||
| Ceramic scaffold bio-functionalized with mesenchymal cells and osteoblasts | Ceramic scaffold is cultured with hMSC and osteoblast to produce ECM and cytokines previous to HSC culture. | MSCs and osteoblasts produced a bone marrow-like environment. Functionalization increased expansion of HSCs capable of hematopoietic reconstitution [61]. |
| Polyethylene glycol (PEG) bio-functionalized hydrogels | PEG-acrylate hydrogel was bio-functionalized by including a modified RGD peptide (involved in ECM-cell adhesion) | Supports CD34+ expansion and stemness better than 2D culture [48]. |
| Bio-derived bone scaffolds (BDBS) | Scaffold from human bone is biofunctionalized with MSCs and osteoblasts. | Supports adhesion, expansion and maintenance of stemness in HSCs better than 2D co-culture [62]. |
| Gelatin-based porous scaffold (Gelfoam) functionalized with several stromal cells | Scaffold was cultured with MSC, endothelial, osteoblasts previous to HSC on the Gel foam. | This functionalized scaffold allowed adhesion and growth of different niche cells. Supported expansion and maintenance of HSC [68]. |
| Natural Materials | ||
| Collagen | Elastic, biodegradable, natural component of the ECM | Co-culture in collagen supports CD34+ differentiation and expansion [69]. |
| Fibrin | Natural protein, highly biocompatible. | Supports CD34+ adherence and proliferation [58]. |
| Cellulose | Abundant, low-cost, non-biodegradable. Could be natural or synthetic. | Cellulose beads did not support CD34+ cell adhesion and proliferation [60]. |
| Microspheres/organoids | ||
| Collagen microspheres | MSCs were encapsulated in collagen microspheres, osteogenic differentiation was induced and subsequent decellularization to use it as scaffold for HSCs culture. | Supported mice HSC and MSC proliferation and adhesion [91]. |
| Mesenspheres | Spheres of a low-adherence population of MSCs formed spontaneously in ultra-low adherent dishes | BM Mesenspheres support expansion of HSC [63] in co-culture. |
| Hematosphere | Peripheral blood mononuclear cells formed spheres in ultra-low attach surfaces. | Spheres formed from PBMNCs support extensive expansion of primitive Lin(−)CD34(+)CD38(−) HSCs [55]. |
| Bone marrow organoid | Cord blood fibroblasts form a cellular pellet, this pellet was differentiated in vitro to a chondroid rudiment. After implantation in mice these rudiments remodeled into a functional BM niche. | The implanted organoid resembled the natural HSC niche. Host cells formed vascular structures and HSC engrafted in the organoid [92]. |
| Decellularized ECM/tissue/organ scaffolds | ||
| Decellularized ECM | Obtained by decellularization of ECM produced by stromal cells in vitro | Enhanced HSC adhesion and expansion of CD34+ cells [57]. |
| Decellularized bovine bone marrow (DeBM) | Detergent-free decellularized bovine bone marrow with highly preserved bone marrow architecture | DeBM supported adhesion, focal localization and proliferation of mesenchymal and HSCs [18]. |
| Decellularized porcine bone marrow | High-hydrostatic Pressurization method for decellularization of BM. Cultured with MSCs. |
Supported MSC growth and differentiation. Implantation in mice induced HSC recruitment [64]. |
| 3D printing | ||
| 3D printing of MSCs-laden alginate-gelatin bioink | HSCs were cultured in a printed 3D scaffold fabricated using a mix of alginate, gelatin and MSCs. | Enhanced expansion and stemness of HSCs. Induced expression of integrins and adhesion [93]. |
| 3D printing model of endosteal and perivascular niches | 3D printing of pasty calcium phosphate cement in cylinder-like format and seeded with osteogenic MSC to emulate the endosteal niche and endothelial cell laden Matrigel to mimic the perivascular niche. | Supported proliferation of CD138+ myeloma cells [94] |