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Reconstitution of the complete rupture in musculotendinous junction using skeletal muscle-derived multipotent stem cell sheet-pellets as a "bio-bond".

ABSTRACT: Background. Significant and/or complete rupture in the musculotendinous junction (MTJ) is a challenging lesion to treat because of the lack of reliable suture methods. Skeletal muscle-derived multipotent stem cell (Sk-MSC) sheet-pellets, which are able to reconstitute peripheral nerve and muscular/vascular tissues with robust connective tissue networks, have been applied as a "bio-bond". Methods. Sk-MSC sheet-pellets, derived from GFP transgenic-mice after 7 days of expansion culture, were detached with EDTA to maintain cell-cell connections. A completely ruptured MTJ model was prepared in the right tibialis anterior (TA) of the recipient mice, and was covered with sheet-pellets. The left side was preserved as a contralateral control. The control group received the same amount of the cell-free medium. The sheet-pellet transplantation (SP) group was further divided into two groups; as the short term (4-8 weeks) and long term (14-18 weeks) recovery group. At each time point after transplantation, tetanic tension output was measured through the electrical stimulation of the sciatic nerve. The behavior of engrafted GFP(+) tissues and cells was analyzed by fluorescence immunohistochemistry. Results. The SP short term recovery group showed average 64% recovery of muscle mass, and 36% recovery of tetanic tension output relative to the contralateral side. Then, the SP long term recovery group showed increased recovery of average muscle mass (77%) and tetanic tension output (49%). However, the control group showed no recovery of continuity between muscle and tendon, and demonstrated increased muscle atrophy, with coalescence to the tibia during 4-8 weeks after operation. Histological evidence also supported the above functional recovery of SP group. Engrafted Sk-MSCs primarily formed the connective tissues and muscle fibers, including nerve-vascular networks, and bridged the ruptured tendon-muscle fiber units, with differentiation into skeletal muscle cells, Schwann cells, vascular smooth muscle, and endothelial cells. Discussion. This bridging capacity between tendon and muscle fibers of the Sk-MSC sheet-pellet, as a "bio-bond," represents a possible treatment for various MTJ ruptures following surgery.

SUBMITTER: Hashimoto H

PROVIDER: S-EPMC4957990 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Loss of vital functions in the somatic motor and sensory nervous systems can be induced by severe peripheral nerve transection with a long gap following trauma. In such cases, autologous nerve grafts have been used as the gold standard, with the expectation of activation and proliferation of graft-concomitant Schwann cells associated with their paracrine effects. However, there are a limited number of suitable sites available for harvesting of nerve autografts due to the unavoidable sacrifice of other healthy functions. To overcome this problem, the potential of skeletal muscle-derived multipotent stem cells (Sk-MSCs) was examined as a novel alternative cell source for peripheral nerve regeneration. Cultured/expanded Sk-MSCs were injected into severely crushed sciatic nerve corresponding to serious neurotmesis. After 4 weeks, engrafted Sk-MSCs preferentially differentiated into not only Schwann cells, but also perineurial/endoneurial cells, and formed myelin sheath and perineurium/endoneurium, encircling the regenerated axons. Increased vascular formation was also observed, leading to a favorable blood supply and waste product excretion. In addition, engrafted cells expressed key neurotrophic and nerve/vascular growth factor mRNAs; thus, endocrine/paracrine effects for the donor/recipient cells were also expected. Interestingly, skeletal myogenic capacity of expanded Sk-MSCs was clearly diminished in peripheral nerve niche. The same differentiation and tissue reconstitution capacity of Sk-MSCs was sufficiently exerted in the long nerve gap bridging the acellular conduit, which facilitated nerve regeneration/reconnection. These effects represent favorable functional recovery in Sk-MSC-treated mice, as demonstrated by good corduroy walking. We also demonstrated that these differentiation characteristics of the Sk-MSCs were comparable to native peripheral nerve-derived cells, whereas the therapeutic capacities were largely superior in Sk-MSCs. Therefore, Sk-MSCs can be a novel/suitable alternative cell source for healthy nerve autografts.

Project description:Injury to the distal musculotendinous T junction (DMTJ) of the biceps femoris is a distinct clinical entity that behaves differently from other hamstring injuries due to its complex, multicomponent anatomy and dual innervation. Injury in this region demonstrates a particularly high rate of recurrence, even with prolonged rehabilitation times.To describe the anatomy of the DMTJ of the biceps femoris and analyze the injury patterns seen on magnetic resonance imaging (MRI) to aid prognosis and rehabilitation and minimize the risk of recurrence.Cross-sectional study; Level of evidence, 3.Acute injury to the DMTJ of the biceps femoris was identified in 106 MRI examinations from 55 patients at a single institution. Each injury was classified as involving the long head, the short head, or both components of the DMTJ, with each component individually graded. Injuries were classified as recurrent if there was a previous MRI demonstrating an acute injury to the DMTJ or if there was scarring present at the site of an acute injury.Of the 106 acute injuries to the DMTJ of the biceps femoris, isolated injury to the long head component was the most common (51%), with both components involved in [round 42.5% to 43%] of cases. Isolated injury to the short head component accounted for 7% of cases. The recurrence rate for reinjury to the DMTJ was 54% in this series. The date of prior injury was known in 45 of 57 recurrent cases, with 34 of these reoccurring within 3 months (76%) and 40 reoccurring within 12 months (89%). The recurrent injury was of a higher grade than the prior injury in 22 of 44 instances (50%), the same grade in 16 instances (36%), and a lower grade in 6 instances (14%). Thus, 86% of recurrent injuries were of the same or higher grade than prior injury.These results suggest that high-risk muscle injuries, such as that to the DMTJ of the biceps femoris, should be evaluated using MRI to determine the structural components involved and to assess the extent and severity of injury.

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Reconstitution of the complete rupture in musculotendinous junction using skeletal muscle-derived multipotent stem cell sheet-pellets as a "bio-bond".

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