Mesenchymal stem cells (MSCs) hold many advantages over embryonic stem cells (ESCs) and other somatic cells in clinical applications. MSCs are multipotent cells with strong immunosuppressive properties. They can be harvested from various locations in the human body (e.g., bone marrow and adipose tissues). Cryopreservation represents an efficient method for the preservation and pooling of MSCs, to obtain the cell counts required for clinical applications, such as cell-based therapies and regenerative medicine. Upon cryopreservation, it is important to preserve MSCs functional properties including immunomodulatory properties and multilineage differentiation ability. Further, a biosafety evaluation of cryopreserved MSCs is essential prior to their clinical applications. However, the existing cryopreservation methods for MSCs are associated with notable limitations, leading to a need for new or improved methods to be established for a more efficient application of cryopreserved MSCs in stem cell-based therapies. We review the important parameters for cryopreservation of MSCs and the existing cryopreservation methods for MSCs. Further, we also discuss the challenges to be addressed in order to preserve MSCs effectively for clinical applications.
Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast differentiation independently of pore size. Substrate at a stiffness of 30 kPa, which mimics the stiffness of native fibrotic cardiac tissue, was found to induce cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model. Conditioned medium of hMSCs was applied to the model to determine its role and inhibitory mechanism on cardiac myofibroblast differentiation. It was found that hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast differentiation via downregulation of angiotensin II type 1 receptor (AT1R) and upregulation of Smad7. These findings would aid in establishment of the therapeutic use of hMSCs in cardiac fibrosis therapy in future.
The need to have a better and safer culture condition for expansion of human mesenchymal stem cells (MSCs) is crucial particularly to prevent infection and immune rejection. This is normally associated with the use of animal-based serum in the culture media for cell expansion. The aim of this study is to investigate alternative culture conditions which may provide better and safer environment for cell growth. In the present study, human adipose-derived stem cells (ASCs) at passage 3 were subjected to treatment in 4 conditions: (1) 21 % O2 with fetal bovine serum (FBS), (2) 21 % O2 without FBS, (3) 2 % O2 with FBS and (4) 2 % O2 without FBS followed by subsequent analysis of their phenotype, viability and functionality. We observed that ASCs cultured in all conditions present no significant phenotypic changes. It was found that ASCs cultured in 2 % O2 without serum showed an increase in viability and growth to a certain extent when compared to those cultured in 21 % O2 without serum. However, ASCs cultured in 2 % O2 without serum displayed a relatively low adipogenic and osteogenic potential. On the other hand, interestingly, there was a positive enhancement in chondrogenic differentiation of ASCs cultured in 21 % O2 without serum. Our findings suggest that different culture conditions may be suitable for different indications. In summary, ASCs cultured in serum-free condition can still survive, proliferate and undergo subsequent adipogenic, osteogenic and chondrogenic differentiation. Therefore, FBS is feasible to be excluded for culture of ASCs, which avoids clinical complications.
The response of human skin to "stress relaxation" tests at low loads in vitro was investigated. A number of behaviours, other than those already well established and documented, were observed. The significant behaviours are pure recovery and relaxation-recovery. Other behaviours observed are temporary stress recovery during the relaxation process, and momentary sudden non-linear drop in stress value followed by a second relaxation. The pure recovery and relaxation-recovery responses are repeatable. The latter represents the transitional response between the well-known behaviour of stress relaxation and the behaviour of stress recovery.
The response of human skin to biaxial stretch tests in vivo was investigated and compared to the response to uniaxial tension. The results obtained illustrate the nonlinear, anisotropic, and viscoelastic (time-dependent) properties of skin under biaxial stretch. Preconditioning in the load-extension response was found not to be prominent. The results also suggest that the response of skin to a biaxial stretch in vivo is qualitatively similar to that in vitro. Values of the terminal stiffness and limit strain of skin under a biaxial stretch are found.
Local strains acting across an area of skin loaded uniaxially in vivo are converted to stresses using the standard elastic formulae. The stress values are compared to those obtained using the classical Bossinesq and Michell stress functions. The results indicate that these functions are capable of describing the response of the skin, both in the low load and the high load regions.
The deep tendon reflex assessments that are essential to the accurate diagnosis of neurological or neuromuscular disorders are conducted subjectively in clinical neurology. Our aim was to assess deep tendon reflexes objectively with a new reflex quantification method.
Socket is an important part of every prosthetic limb as an interface between the residual limb and prosthetic components. Biomechanics of socket-residual limb interface, especially the pressure and force distribution, have effect on patient satisfaction and function. This paper aimed to review and evaluate studies conducted in the last decades on the design of socket, in-socket interface pressure measurement, and socket biomechanics. Literature was searched to find related keywords with transtibial amputation, socket-residual limb interface, socket measurement, socket design, modeling, computational modeling, and suspension system. In accordance with the selection criteria, 19 articles were selected for further analysis. It was revealed that pressure and stress have been studied in the last decaeds, but quantitative evaluations remain inapplicable in clinical settings. This study also illustrates prevailing systems, which may facilitate improvements in socket design for improved quality of life for individuals ambulating with transtibial prosthesis. It is hoped that the review will better facilitate the understanding and determine the clinical relevance of quantitative evaluations.
This study focused on developing a 3D finite element model of functionally graded femoral prostheses to decrease stress shielding and to improve total hip replacement performance. The mechanical properties of the modeled functionally graded femoral prostheses were adjusted in the sagittal and transverse planes by changing the volume fraction gradient exponent. Prostheses with material changes in the sagittal and transverse planes were considered longitudinal and radial prostheses, respectively. The effects of cemented and noncemented implantation methods were also considered in this study. Strain energy and von Mises stresses were determined at the femoral proximal metaphysis and interfaces of the implanted femur components, respectively. Results demonstrated that the strain energy increased proportionally with increasing volume fraction gradient exponent, whereas the interface stresses decreased on the prostheses surfaces. A limited increase was also observed at the surfaces of the bone and cement. The periprosthetic femur with a noncemented prosthesis exhibited higher strain energy than with a cemented prosthesis. Radial prostheses implantation displayed more strain energy than longitudinal prostheses implantation in the femoral proximal part. Functionally graded materials also increased strain energy and exhibited promising potentials as substitutes of conventional materials to decrease stress shielding and to enhance total hip replacement lifespan.
Circulating tumor cells (CTCs) are tumor cells that have detached from primary tumor site and are transported via the circulation system. The importance of CTCs as prognostic biomarker is leveraged when multiple studies found that patient with cutoff of 5 CTCs per 7.5 mL blood has poor survival rate. Despite its clinical relevance, the isolation and characterization of CTCs can be quite challenging due to their large morphological variability and the rare presence of CTCs within the blood. Numerous methods have been employed and discussed in the literature for CTCs separation. In this paper, we will focus on label free CTCs isolation methods, in which the biophysical and biomechanical properties of cells (e.g., size, deformability, and electricity) are exploited for CTCs detection. To assess the present state of various isolation methods, key performance metrics such as capture efficiency, cell viability, and throughput will be reported. Finally, we discuss the challenges and future perspectives of CTC isolation technologies.
Postural control has been widely evaluated for the normal population and different groups over the past 20 years. Numerous studies have investigated postural control in quiet standing posture among amputees. However, a comprehensive analysis is lacking on the possible contributing factors to balance. The present systematic review highlights the current findings on variables that contribute to balance instability for lower extremity amputees. The search strategy was performed on PubMed, Web of Science, Medline, Scopus, and CINAHL and then followed by additional manual searching via reference lists in the reviewed articles. The quality of the articles was evaluated using a methodological quality assessment tool. This review included and evaluated a total of 23 full-text articles. Despite the inconsistencies in the methodological design of the studies, all articles scored above the acceptable level in terms of quality. A majority of the studies revealed that lower extremity amputees have increased postural sway in the standing posture. Asymmetry in body weight, which is mainly distributed in the non-amputated leg, was described. Aside from the centre of pressure in postural control, sensory inputs may be a related topic for investigation in view of evidence on their contribution, particularly visual input. Other balance-related factors, such as stump length and patients' confidence level, were also neglected. Further research requires examination on the potential factors that affect postural control as the information of standing postural is still limited.
Postural stability is crucial in maintaining body balance during quiet standing, locomotion, and any activities that require a high degree of balance performance, such as participating in sports and dancing. Research has shown that there is a relationship between stability and body mass. The aims of this study were to examine the impact that two variables had on static postural control: body mass index (BMI) and gender. Eighty healthy young adults (age=21.7±1.8 yr; height=1.65±0.09 m; mass=67.5±19.0 kg) participated in the study and the static postural control was assessed using the Biodex Balance System, with a 20 Hz sampling rate in the bipedic stance (BLS) and unipedic stance (ULS) for 30s. Five test evaluations were performed for each balance test. Postural control was found to be negatively correlated with increased adiposity, as the obese BMI group performed significantly poorer than the underweight, normal weight and overweight groups during BLS and ULS tests. The underweight, normal weight and overweight groups exhibited greater anterior-posterior stability in postural control during quiet stance. In addition, female displayed a trend of having a greater postural sway than male young adults, although it was evidenced in only some BMI groups. This study revealed that BMI do have an impact on postural control during both BLS and ULS. As such, BMI and gender-specific effects should be taken into consideration when selecting individuals for different types of sporting activities, especially those that require quiet standing.
Postural balance is vital for safely carrying out many daily activities, such as locomotion. The purpose of this study was to determine how changes in normal standing (NS) and standing with toe-extension (SWT) impact postural control during quiet standing. Furthermore, the research aimed to examine the extent to which the effect of these factors differed between genders.
Balance is essential for mobility and performing activities of daily living. People with knee osteoarthritis display impairment in knee joint proprioception. Thus, the aim of this study was to evaluate balance and risk of fall in individuals with bilateral mild and moderate knee osteoarthritis. Sixty subjects aged between 50 and 70 years volunteered in this study. They were categorized into three groups which were healthy (n = 20), mild (n = 20) and moderate (n = 20) bilateral knee osteoarthritis groups. Dynamic and static balance and risk of fall were assessed using Biodex Stability System. In addition, Timed Up and Go test was used as a clinical test for balance. Results of this study illustrated that there were significant differences in balance (dynamic and static) and risk of fall between three groups. In addition, the main (most significant) difference was found to be between healthy group and moderate group. Furthermore, on clinical scoring of balance, the "Timed Up and Go" test, all three groups showed significant difference. In conclusion, bilateral knee osteoarthritis impaired the balance and increased the risk of fall, particularly in people with moderate knee osteoarthritis.
The knee adduction moment represents the medial knee joint load, and greater value is associated with higher load. In people with knee osteoarthritis, it is important to apply proper treatment with the least side effects to reduce knee adduction moment and, consequently, reduce medial knee joint load. This reduction may slow the progression of knee osteoarthritis. The research team performed a literature search of electronic databases. The search keywords were as follows: knee osteoarthritis, knee adduction moment, exercise program, exercise therapy, gait retraining, gait modification and knee joint loading. In total, 12 studies were selected, according to the selection criteria. Findings from previous studies illustrated that exercise and gait retraining programs could alter knee adduction moment in people with knee osteoarthritis. These treatments are noninvasive and nonpharmacological which so far have no or few side effects, as well as being low cost. The results of this review revealed that gait retraining programs were helpful in reducing the knee adduction moment. In contrast, not all the exercise programs were beneficial in reducing knee adduction moment. Future studies are needed to indicate best clinical exercise and gait retraining programs, which are most effective in reducing knee adduction moment in people with knee osteoarthritis.
Study design: systematic review
This paper describes the water compartments in healthy subjects and dengue patients on the day of defervescence of fever using bioelectrical impedance analysis. A total of 223 healthy subjects (65 males and 158 females) and 210 dengue patients (119 males and 91 females) in Hospital Universiti Kebangsaan Malaysia (HUKM), were studied. The ages for healthy subjects vary between 14 and 60 years old with mean age of 26.05 years while the ages for the dengue patients vary between 12 and 83 years old with mean age of 30.14 years. The parameters of water compartments investigated were total body water (TBW), extracellular water (ECW) and intracellular water (ICW). There were significant difference between healthy subjects and dengue patients for both male (p<0.05) and female (p<0.001) beginning on fever day 0 till fever day 4. The mean TBW and ECW values of dengue patients obtained were found to be higher than the normal healthy subjects while the mean ICW was lower. The mean TBW and ICW for male were higher than female while the mean ECW for male was lower than female for healthy subjects and dengue patients.
This paper describes a model for predicting hemoglobin (Hb) by using bioelectrical impedance analysis (BIA) in dengue patients in the Hospital Universiti Kebangsaan Malaysia (HUKM). Bioelectrical impedance measurements were conducted on 83 (47 males and 36 females) serologically confirmed dengue fever (DF) and dengue hemorrhagic fever (DHF) patients during their hospitalization. The predictive equation for Hb was derived using multivariate analysis. We investigated all the parameters in BIA, patients' symptom and demographic data. In this developed model, four predictors (reactance (XC), sex, weight and vomiting) were found to be the best predictive factors for modeling Hb in dengue patients. However, the model can only explain approximately 42% of the variation in Hb status, thus single frequency bio-impedance stand-alone technique is insufficient to monitor Hb for the DF and DHF patients. Further investigation using multi-frequency BIA is recommended in modeling Hb to achieve the most parsimonious model.
Good prosthetic suspension system secures the residual limb inside the prosthetic socket and enables easy donning and doffing. This study aimed to introduce, evaluate and compare a newly designed prosthetic suspension system (HOLO) with the current suspension systems (suction, pin/lock and magnetic systems).
Good suspension lessens the pistoning (vertical displacement) of the residual limb inside the prosthetic socket. Several methods are used for measuring the pistoning.
The effects of Seal-In X5 and Dermo liner (Össur) on suspension and patient's comfort in lower limb amputees are unclear. In this report, we consider the case of a 51-yr-old woman with bilateral transtibial amputation whose lower limbs were amputated because of peripheral vascular disease. The subject had bony and painful residual limbs, especially at the distal ends. Two prostheses that used Seal-In X5 liners and a pair of prostheses with Dermo liners were fabricated, and the subject wore each for a period of 2 wks. Once the 2 wks had passed, the pistoning within the socket was assessed and the patient was questioned as to her satisfaction with both liners. This study revealed that Seal-In X5 liner decreased the residual limb pain experienced by the patient and that 1-2 mm less pistoning occurred within the socket compared with the Dermo liner. However, the patient needed to put in extra effort for donning and doffing the prosthesis. Despite this, it is clear that the Seal-In X5 liner offers a viable alternative for individuals with transtibial amputations who do not have enough soft tissue around the bone, especially at the end of the residual limb.