Neuronal Commitment of Human Circulating Multipotent Cells By Carbon nanotube-polymer Scaffolds and Biomimetic Peptides

Scapin, Giorgia; Bertalot, Thomas; Vicentini, Nicola; Gatti, Teresa; Tescari, Simone; Filippis, Vincenzo De; Marega, Carla; Menna, Enzo; Gasparella, Marco; Parnigotto, Pier Paolo; Liddo, Rosa Di; Filippini, F.

doi:10.2217/nnm-2016-0150

Cited by 22 publications

(31 citation statements)

References 60 publications

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“…A), suggesting a possible correlation among in vivo regeneration following the implantation of CLP‐MB and the in vitro development of cells with anti‐inflammatory functionality, proliferative activity and high grade of stemness. In particular, CPL‐CMC subcultures from 4th to 20th generation demonstrated a doubling population time of 21 ± 1.85 hrs, which was significantly shorter than that of other multipotent cells isolated from human peripheral blood (Fig. B).…”

Section: Resultsmentioning

confidence: 89%

“…Opening new perspectives in autologous stem cell research, L-PRF products prepared according to Caloprisco's method [10] have been found to deliver stem cell-like cells with unique phenotypic features, functionality and differentiative potentialities in comparison with endothelial/haematopoietic progenitors [29,30], mesenchymal stem cells (MSCs) [27,31,32], embryonic-like stem cells [11,[33][34][35][36] and circulating multipotent cells [12,13,25,37]. Isolated by minimal in vitro manipulation of CPL membranes, CMC cells showed fibroblast-like morphology, long-lasting proliferative activity and high expression of CD44/HCELL, CD49f and CXCR4.…”

Section: Discussionmentioning

confidence: 99%

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Leucocyte and Platelet‐rich Fibrin: a carrier of autologous multipotent cells for regenerative medicine

Liddo

Bertalot

Borean

et al. 2018

J Cellular Molecular Medi

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The wound healing is a complex process wherein inflammation, proliferation and regeneration evolve according to a spatio‐temporal pattern from the activation of coagulation cascade to the formation of a plug clot including fibrin matrix, blood‐borne cells and cytokines/growth factors. Creating environments conducive to tissue repair, the haemoderivatives are commonly proposed for the treatment of hard‐to‐heal wounds. Here, we explored in vitro the intrinsic regenerative potentialities of a leucocyte‐ and platelet‐rich fibrin product, known as CPL‐MB, defining the stemness grade of cells sprouting from the haemoderivative. Using highly concentrated serum‐based medium to simulate wound conditions, we isolated fibroblast‐like cells (CPL‐CMCs) adhering to plastic and showing stable in vitro propagation, heterogeneous stem cell expression pattern, endothelial adhesive properties and immunomodulatory profile. Due to their blood derivation and expression of CXCR4, CPL‐CMCs have been suggested to be immature cells circulating in peripheral blood at quiescent state until activation by both coagulation event and inflammatory stimuli such as stromal‐derived factor 1/SDF1. Expressing integrins (CD49f, CD103), vascular adhesion molecules (CD106, CD166), endoglin (CD105) and remodelling matrix enzymes (MMP2, MMP9, MMP13), they showed a transendothelial migratory potential besides multipotency. Taken together, our data suggested that a standardized, reliable and economically feasible blood product such as CPL‐MB functions as an artificial stem cell niche that, under permissive conditions, originate ex vivo immature cells that could be useful for autologous stem cell‐based therapies.

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Section: Resultsmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Leucocyte and Platelet‐rich Fibrin: a carrier of autologous multipotent cells for regenerative medicine

Liddo

Bertalot

Borean

et al. 2018

J Cellular Molecular Medi

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“…Mesenchymal stem cells (MSCs) and fat-derived stem cells are widely used for regenerative-medicine purposes [5][6][7]. Among blood-derived stem cells, human circulating multipotent stem cells (hCMCs) [8] represent an interesting model as they can differentiate into progenitors for several mesenchymal tissue types, such as adipocytes, osteoblasts, chondroblasts, or muscle cells in response to different culture conditions. These cells are extremely sensitive to changes in the microenvironment, and respond to biomimetic stimuli by sudden variations in gene expression; importantly, when specific growth factors are added, they can also commit to neuronal differentiation [9].…”

Section: Introductionmentioning

confidence: 99%

“…Conductive CNTs represent an established nanofiller for boosting neuronal commitment and differentiation [15][16][17][18][19][20]. FDA-approved poly(L-lactic) acid (PLLA) is widely used in regenerative medicine, and scaffolds consisting of CNTs dispersed in a PLLA matrix (CNT@PLLA) were able to commit hCMCs toward a neuronal lineage even in the absence of exogenous neurotrophins, highlighting their biomimetic potential [8].…”

Section: Introductionmentioning

confidence: 99%

Commitment of Autologous Human Multipotent Stem Cells on Biomimetic Poly-L-Lactic Acid-Based Scaffolds Is Strongly Influenced by Structure and Concentration of Carbon Nanomaterial

et al. 2020

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Nanocomposite scaffolds combining carbon nanomaterials (CNMs) with a biocompatible matrix are able to favor the neuronal differentiation and growth of a number of cell types, because they mimic neural-tissue nanotopography and/or conductivity. We performed comparative analysis of biomimetic scaffolds with poly-L-lactic acid (PLLA) matrix and three different p-methoxyphenyl functionalized carbon nanofillers, namely, carbon nanotubes (CNTs), carbon nanohorns (CNHs), and reduced graphene oxide (RGO), dispersed at varying concentrations. qRT-PCR analysis of the modulation of neuronal markers in human circulating multipotent cells cultured on nanocomposite scaffolds showed high variability in their expression patterns depending on the scaffolds’ inhomogeneities. Local stimuli variation could result in a multi- to oligopotency shift and commitment towards multiple cell lineages, which was assessed by the qRT-PCR profiling of markers for neural, adipogenic, and myogenic cell lineages. Less conductive scaffolds, i.e., bare poly-L-lactic acid (PLLA)-, CNH-, and RGO-based nanocomposites, appeared to boost the expression of myogenic-lineage marker genes. Moreover, scaffolds are much more effective on early commitment than in subsequent differentiation. This work suggests that biomimetic PLLA carbon-nanomaterial (PLLA-CNM) scaffolds combined with multipotent autologous cells can represent a powerful tool in the regenerative medicine of multiple tissue types, opening the route to next analyses with specific and standardized scaffold features.

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“…37,38 While processing the peripheral blood of Vietnamese pigs (VPs) sedated before heart valve surgery, we recently isolated a population of multipotent adherent cells that fulfill some MSC criteria, as defined by the International Society for Cellular Therapy. 29 Due to similarities with human circulating cells previously described, 38 we have named these cells "porcine circulating multipotent cells" (pCMC) and experimentally used to explore the repopulation potential of porcine heart valves decellularized with TriCol procedure (Figure 1). Under no-flow culture condition, pCMC have been showed to be differentially stimulated by AVL and PVL and expressed gene markers correlatable to VIC-and VEC-like phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Nanopatterned acellular valve conduits drive the commitment of blood-derived multipotent cells

Liddo¹,

Andrea²,

Barbon³

et al. 2016

IJN

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Considerable progress has been made in recent years toward elucidating the correlation among nanoscale topography, mechanical properties, and biological behavior of cardiac valve substitutes. Porcine TriCol scaffolds are promising valve tissue engineering matrices with demonstrated self-repopulation potentiality. In order to define an in vitro model for investigating the influence of extracellular matrix signaling on the growth pattern of colonizing blood-derived cells, we cultured circulating multipotent cells (CMC) on acellular aortic (AVL) and pulmonary (PVL) valve conduits prepared with TriCol method and under no-flow condition. Isolated by our group from Vietnamese pigs before heart valve prosthetic implantation, porcine CMC revealed high proliferative abilities, three-lineage differentiative potential, and distinct hematopoietic/endothelial and mesenchymal properties. Their interaction with valve extracellular matrix nanostructures boosted differential messenger RNA expression pattern and morphologic features on AVL compared to PVL, while promoting on both matrices the commitment to valvular and endothelial cell-like phenotypes. Based on their origin from peripheral blood, porcine CMC are hypothesized in vivo to exert a pivotal role to homeostatically replenish valve cells and contribute to hetero- or allograft colonization. Furthermore, due to their high responsivity to extracellular matrix nanostructure signaling, porcine CMC could be useful for a preliminary evaluation of heart valve prosthetic functionality

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Neuronal Commitment of Human Circulating Multipotent Cells By Carbon nanotube-polymer Scaffolds and Biomimetic Peptides

Abstract: This work suggests the scaffold-peptides system combined with autologous hCMCs as a functional biomimetic, self-standing prototype for neural regenerative medicine applications.

Cited by 22 publications

References 60 publications

Leucocyte and Platelet‐rich Fibrin: a carrier of autologous multipotent cells for regenerative medicine

Leucocyte and Platelet‐rich Fibrin: a carrier of autologous multipotent cells for regenerative medicine

Commitment of Autologous Human Multipotent Stem Cells on Biomimetic Poly-L-Lactic Acid-Based Scaffolds Is Strongly Influenced by Structure and Concentration of Carbon Nanomaterial

Nanopatterned acellular valve conduits drive the commitment of blood-derived multipotent cells

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