To assess the safety and therapeutic efficacy of autologous human bone marrow cell (BMC) transplantation and the administration of granulocyte macrophage-colony stimulating factor (GM-CSF), a phase I/II open-label and nonrandomized study was conducted on 35 complete spinal cord injury patients. The BMCs were transplanted by injection into the surrounding area of the spinal cord injury site within 14 injury days (n ‫؍‬ 17), between 14 days and 8 weeks (n ‫؍‬ 6), and at more than 8 weeks (n ‫؍‬ 12) after injury. In the control group, all patients (n ‫؍‬ 13) were treated only with conventional decompression and fusion surgery without BMC transplantation. The patients underwent preoperative and follow-up neurological assessment using the American Spinal Injury Association Impairment Scale (AIS), electrophysiological monitoring, and magnetic resonance imaging (MRI). The mean follow-up period was 10.4 months after injury. At 4 months, the MRI analysis showed the enlargement of spinal cords and the small enhancement of the cell implantation sites, which were not any adverse lesions such as malignant transformation, hemorrhage, new cysts, or infections. Furthermore, the BMC transplantation and GM-CSF administration were not associated with any serious adverse clinical events increasing morbidities. The AIS grade increased in 30.4% of the acute and subacute treated patients (AIS A to B or C), whereas no significant improvement was observed in the chronic treatment group. Increasing neuropathic pain during the treatment and tumor formation at the site of transplantation are still remaining to be investigated. Long-term and large scale multicenter clinical study is required to determine its precise therapeutic effect.

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Abstract:The importance of scaffold biomaterials has been emphasized for in vitro culture of tissue-engineered cartilage in a three-dimensional (3D) environment. In this study, we examined the feasibility of fibrin glue, mixed with hyaluronic acid (HA) as a composite scaffold. Fibrin glue has been a useful cell delivery matrix for cartilage tissue engineering and HA is a key component of normal articular cartilage. Our hypothesis is that compared to fibrin itself, a fibrin/HA composite can have significantly enhanced properties, due mainly to the added benefits of HA in the matrix. Pieces of cartilage were isolated from rabbit knees and the chondrocytes were harvested through enzymatic digestion. Both fibrin and fibrin/HA composite were prepared and subsequently implanted in nude mice (n = 9, each group) for 1, 2, and 4 weeks, respectively. The retrieved specimens were then analyzed and the results were compared. Cartilage-like tissue formation was detected earlier with fibrin/HA specimens. They produced significantly higher amounts of the extracellular matrix (ECM) molecules, GAG, and collagen at each time point than those in fibrin. Interestingly, the fibrin/HA composite was also competent in maintaining its initial size. Histology-Safranin O/fast green and Alcian blue-of the retrieved specimens found more intense, uniform staining in the fibrin/HA composites. Analysis of the gene expression of the ECM molecules also confirmed the benefits of the composite with added HA in the maintenance of phenotypic stability. The present study suggests that fibrin/HA composite may serve as a dependable cell delivery vehicle as well as a structural basis for tissue-engineered cartilage. Key Words: Cartilage-Chondrocyte-Tissue engineering-Fibrin/hyaluronic acid composite-Fibrin.Biodegradable polymers have been one of the key components in cartilage tissue engineering. These polymers in the form of gel, sponge, and fiber serve as a scaffold in which chondrocytes are able to proliferate and differentiate. This technology allows cell/ polymer constructs to be implanted into cartilage defects and results in successful engraftment and new cartilage formation. General requirements of scaffolds are that they are 3D, highly porous with an interconnected pore network, biodegradable, and biocompatible. They should also carry appropriate surface properties for cell adhesion, proliferation, and differentiation. Proper mechanical properties are also required. Along with the synthetic scaffolds, many naturally derived scaffolds have been developed and examined in vitro and/or in vivo, including hyaluronate (HA) (1-3), fibrin (4-6), collagen (7), alginate (8,9), and chitosan (10). Although these materials have met those criteria in vitro, hyaline cartilage tissue formation is still challenging.It has been common practice that two or more biomaterials are combined to utilize the benefits of each biomaterial. Matrix engineering by adding various components has been successful to produce a composite matrix, such as fibrin-alginate (11), HAalg...

Mesenchymal stem cells (MSCs) are regarded as a potential autologous source for cartilage repair, because they can differentiate into chondrocytes by transforming growth factor‐beta (TGF‐β) treatment under the 3‐dimensional (3‐D) culture condition. However, more efficient and versatile methods for chondrogenic differentiation of MSCs are still in demand for its clinical application. Recently, low‐intensity ultrasound (LIUS) was shown to enhance fracture healing in vitro and induce chondrogenesis of MSCs in vitro. In this study, we investigated the effects of LIUS on the chondrogenesis of rabbit MSCs (rMSCs) in a 3‐D alginate culture and on the maintenance of chondrogenic phenotypes after replating them on a monolayer culture. The LIUS treatment of rMSCs increased: (i) the matrix formation; (ii) the expression of chondrogenic markers such as collagen type II, aggrecan, and Sox‐9; (iii) the expression of tissue inhibitor of metalloprotease‐2 implicated in the integrity of cartilage matrix; and (iv) the capacity to maintain the chondrogenic phenotypes in a monolayer culture. Notably, LIUS effects were clearly shown even without TGF‐β treatment. These results suggest that LIUS treatment could be an efficient and cost‐effective method to induce chondrogenic differentiation of MSCs in vitro for cartilage tissue engineering.