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Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications

Choi JR, Yong KW, Wan Safwani WKZ

Cell Mol Life Sci, 2017 07;74(14):2587-2600.
PMID: 28224204 DOI: 10.1007/s00018-017-2484-2

Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discuss the influence of hypoxia on the phenotype and functionality of hASCs in terms of viability, stemness, proliferation, differentiation, soluble factor secretion, and biosafety. We provide a glimpse of the possible cellular mechanism that involved under hypoxia and discuss the potential clinical applications. We then highlight the existing challenges and discuss the future perspective on the use of hypoxic-treated hASCs.
Biomechanical and functional efficacy of knee sleeves: A literature review

Mohd Sharif NA, Goh SL, Usman J, Wan Safwani WKZ

Phys Ther Sport, 2017 Nov;28:44-52.
PMID: 28673759 DOI: 10.1016/j.ptsp.2017.05.001

BACKGROUND: Knee sleeves are widely used for the symptomatic relief and subjective improvements of knee problems. To date, however, their biomechanical effects have not been well understood.
OBJECTIVE: To determine whether knee sleeves can significantly improve the biomechanical variables for knee problems.
METHOD: Systematic literature search was conducted on four online databases - PubMed, Web of Science, ScienceDirect and Springer Link - to find peer-reviewed and relevant scientific papers on knee sleeves published from January 2005 to January 2015. Study quality was assessed using the Structured Effectiveness Quality Evaluation Scale (SEQES).
RESULTS: Twenty studies on knee sleeves usage identified from the search were included in the review because of their heterogeneous scope of coverage. Twelve studies found significant improvement in gait parameters (3) and functional parameters (9), while eight studies did not find any significant effects of knee sleeves usage.
CONCLUSION: Most improvements were observed in: proprioception for healthy knees, gait and balance for osteoarthritic knees, and functional improvement of injured knees. This review suggests that knee sleeves can effect functional improvements to knee problems. However, further work is needed to confirm this hypothesis, due to the lack of homogeneity and rigor of existing studies.
Biosafety and bioefficacy assessment of human mesenchymal stem cells: what do we know so far?

Yong KW, Choi JR, Dolbashid AS, Wan Safwani WKZ

Regen Med, 2018 03;13(2):219-232.
PMID: 29509072 DOI: 10.2217/rme-2017-0078

An outstanding amount of resources has been used in research on manipulation of human stem cells, especially mesenchymal stem cells (MSCs), for various clinical applications. However, human MSCs have not been fully utilized in clinical applications due to restrictions with regard to their certain biosafety and bioefficacy concerns, for example, genetic abnormality, tumor formation, induction of host immune response and failure of homing and engraftment. This review summarizes the biosafety and bioefficacy assessment of human MSCs in terms of genetic stability, tumorigenicity, immunogenicity, homing and engraftment. The strategies used to reduce the biosafety concerns and improve the bioefficacy of human MSCs are highlighted. In addition, the approaches that can be implemented to improve their biosafety and bioefficacy assessment are briefly discussed.
Hypoxia enhances the viability, growth and chondrogenic potential of cryopreserved human adipose-derived stem cells

Wan Safwani WKZ, Choi JR, Yong KW, Ting I, Mat Adenan NA, Pingguan-Murphy B

Cryobiology, 2017 04;75:91-99.
PMID: 28108309 DOI: 10.1016/j.cryobiol.2017.01.006

Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs) for clinical use. However, cryopreservation has been shown to be detrimental to ASCs, particularly in term of cell viability. To restore the viability of cryopreserved ASCs, it is proposed to culture the cells in a hypoxic condition. To this end, we aim to investigate the effect of hypoxia on the cryopreserved human ASCs in terms of not only cell viability, but also their growth and stemness properties, which have not been explored yet. In this study, human ASCs were cultured under four different conditions: fresh (non-cryopreserved) cells cultured in 1) normoxia (21% O2) and 2) hypoxia (2% O2) and cryopreserved cells cultured in 3) normoxia and 4) hypoxia. ASCs at passage 3 were subjected to assessment of viability, proliferation, differentiation, and expression of stemness markers and hypoxia-inducible factor-1 alpha (HIF-1α). We found that hypoxia enhances the viability and the proliferation rate of cryopreserved ASCs. Further, hypoxia upregulates HIF-1α in cryopreserved ASCs, which in turn activates chondrogenic genes to promote chondrogenic differentiation. In conclusion, hypoxic-preconditioned cryopreserved ASCs could be an ideal cell source for cartilage repair and regeneration.
Effects of simple knee sleeves on pain and knee adduction moment in early unilateral knee osteoarthritis

Mohd Sharif NA, Usman J, Wan Safwani WKZ, Siew Li G, Abdul Karim S, Mohamed NA, et al.

Proc Inst Mech Eng H, 2019 Nov;233(11):1132-1140.
PMID: 31597554 DOI: 10.1177/0954411919874614

Knee sleeves are often prescribed to alleviate pain in people with early knee osteoarthritis. However, the biomechanics underlying their pain-relieving effect are still not well understood. This pre-post study aims at evaluating and comparing the effects of two different types of knee sleeves on knee adduction moment. Patients with clinically diagnosed knee osteoarthritis were recruited from the University of Malaya Medical Centre and were randomly assigned to two test groups using (1) a simple knee sleeve and (2) a simple sleeve with patella cutout. Knee adduction moment was collected using the Vicon motion capture system with two Kistler force plates. Pain, stiffness and physical functions were recorded using the Western Ontario and McMaster Universities Osteoarthritis Index. All measurements were taken before, immediately after and at the completion of 6 weeks of application (primary time point). In total, 17 participants with early unilateral knee osteoarthritis (47.7 (9.7) years) completed the study. Overall results show significant reduction in pain, early stance and late stance knee adduction moment and increased walking speed after 6 weeks of both knee sleeves application. This study results suggest that knee sleeves can reduce knee adduction moments in early unilateral knee osteoarthritis by 14.0% and 12.1% using the simple sleeve and the sleeve with patella cutout, respectively, and can potentially delay disease progression. In addition, knee sleeve with patella cutout does not provide additional benefits when compared to the simple knee sleeve.