Novel Strategy to Engineer Trachea Cartilage Graft With Marrow Mesenchymal Stem Cell Macroaggregate and Hydrolyzable Scaffold

Abstract

Limited donor sites of cartilage and dedifferentiation of chondrocytes during expansion, low tissue reconstruction efficiency, and uncontrollable immune reactions to foreign materials are the main obstacles to overcome before cartilage tissue engineering can be widely used in the clinic. In the current study, we developed a novel strategy to fabricate tissue-engineered trachea cartilage grafts using marrow mesenchymal stem cell (MSC) macroaggregates and hydrolyzable scaffold of polylactic acid-polyglycolic acid copolymer (PLGA). Rabbit MSCs were continuously cultured to prepare macroaggregates in sheet form. The macroaggregates were studied for their potential for chondrogenesis. The macroaggregates were wrapped against the PLGA scaffold to make a tubular composite. The composites were incubated in spinner flasks for 4 weeks to fabricate trachea cartilage grafts. Histological observation and polymerase chain reaction array showed that MSC macroaggregates could obtain the optimal chondrogenic capacity under the induction of transforming growth factor-beta. Engineered trachea cartilage consisted of evenly spaced lacunae embedded in a matrix rich in proteoglycans. PLGA scaffold degraded totally during in vitro incubation and the engineered cartilage graft was composed of autologous tissue. Based on this novel, MSC macroaggregate and hydrolyzable scaffold composite strategy, ready-to-implant autologous trachea cartilage grafts could be successfully fabricated. The strategy also had the advantages of high efficiency in cell seeding and tissue regeneration, and could possibly be used in future in vivo experiments.

The Graft of Autologous Adipose-Derived Stem Cells in the Corneal Stromal after Mechanic Damage

“…More importantly, co-expression of ALDH1A1 and keratocan was found in GFP labeled rASCs respectively, which demonstrated that surviving rASCs differentiated to the keratocyte phenotype. These results are consistent with a recent study by Liu et al in which they injected umbilical MSCs into the corneal stroma of lum-mice and found that these implanted cells assumed a keratocyte-like phenotype after implantation [30]. It has been speculated that complicated local environmental cues in the cornea, including growth factors, extracellular matrix and cell-cell interactions, may modulate the differentiation of stem cells into the keratocyte phenotype.…”

“…Thus, we developed a method of seeding cells into a degradable scaffold, which could overcome the drawbacks of cell suspension injection. As a commonly used biomaterial, PLGA has been successfully applied in the fabrication of engineered tissue, such as bladder, cartilage and blood vessels [22,29,30]. Gomes et al [31] reported that they reconstructed cornea with tissue-engineered cell sheets composed of human immature dental pulp stem cells (hIDPSC) in a limbal stem cell deficiency rabbit model.…”

Endogenous and exogenous stem cells: a role in lung repair and use in airway tissue engineering and transplantation

“…Bone marrow-derived populations of MSCs, such as bone marrow-derived chondrocytes, were widely co-cultivated with respiratory epithelial cells to reconstitute artificially fabricated trachea constructs based on synthetic [27], composite [28], or natural decellularized matrixes [3,29]. A tissue-engineered trachea seeded with bone marrow-derived chondrocytes and airway epithelial cells was successfully implanted into a human recipient [3].…”

Using polymeric materials to control stem cell behavior for tissue regeneration

“…To develop a stable and efficient strategy for directing differentiation of stem cells into a chondrogenic lineage, various material design approaches have been investigated (Anderson et al, 2011; Heymer et al, 2009; Lim et al, 2011; Liu et al, 2010a; Park et al, 2011b), including manipulating polymeric substrate properties such as macromer density, supplementing growth and differentiation factors into the polymeric substrate or coating, immobilizing signaling factors on the polymer surface, and making polymer composites.…”

“…For example, TGF-β1 can be encapsulated with adipose-derived stem cells into carrageenan-based hydrogels to enhance chondrogenic differentiation (Rocha et al, 2011). A coupling of TGF-β1 with marrow mesenchymal stem cell macroaggregates in sheet form and wrapped against a PLGA scaffold also forms cartilaginous tissue (Liu et al, 2010a). Another interesting strategy of using TGF-β1 is to incorporate growth factor-loaded PLGA polymer microspheres within hMSC aggregates themselves.…”