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البحوث المنشورة

البحث (1):

عنوان البحث:

Low dose effect of bisphosphonates on hMSCs osteogenic response to titanium surface in vitro

رابط إلى البحث:

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تاريخ النشر:

16/02/2017

موجز عن البحث:

Since the 1980s, titanium (Ti) implants have been routinely used to replace missing teeth. This success is mainly due to the good biocompatibility of Ti and the phenomenon of osseointegration, with very early events at implant placement being important in determining good osseointegration. However, enhancing implant performance with coatings such as hydroxyapatite (HA) and calcium phosphate has proved largely unsuccessful. Human mesenchymal stem cells (hMSCs) are the first osteogenic cells to colonise implant surfaces and offer a target for enhancing osseointegration. We previously reported that small doses of bisphosphonate (BP) may play an integral role in enhancing hMSC proliferation and osteogenic differentiation. The aim of this study is to investigate whether small doses of bisphosphonates enhance proliferation and osteogenic differentiation of hMSCs on Ti surfaces, to enhance bone osseointegration and to accelerate wound healing around the implant surface. Our data suggests that treating cells with small doses of BP (100 nM & 10 nM) induces significant hMSC stimulation of osteogenic markers including calcium, collagen type I and ALP compared to control group on titanium surfaces (P < 0.05). In addition, cell proliferation and migration were significantly enhanced on titanium surfaces (P < 0.05). 

المؤتمرات العلمية:

المؤتمر (1):

عنوان المؤتمر:

9^th Saudi Students’ Conference

تاريخ الإنعقاد:

13-14/02/2016

مكان الإنعقاد:

Birmingham, UK

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Stem Cell Behaviour Following a Single Dose of Bisphosphonate Treatment”

ملخص المشاركة:

Background:

Bisphosphonates (BPs) are analogues of pyrophosphate. They have been used to treat bone diseases characterized by excessive bone resorption such as osteoporosis and malignant bone diseases. It is well known that bisphosphonates inhibit bone resorption by interfering with osteoclasts activity (1). We have previously shown that a small dose of BPs may enhance hMSCs proliferation and osteogenic differentiation(2). In this study we have investigated the long-term effect of a single low dose of BPs on hMSCs proliferative and osteogenic behaviour.

Methods:

In this study we investigated the single dose effect of two types BPs (alendronate and pamidronate) on hMSCs behavior. hMSCs were plated at a density of 5 × 105 cells/75cm2 flasks containing MSC growth media with 10% FCS, 2 mmol L-glutamine and 100U/ml each of penicillin/streptomycin and incubated at 37ºC in humidified 5% CO2. The following day the medium was changed with growth media containing two concentrations of BPs 100nM and 10nM and incubated for 24h. The cells were then washed and trypsinized and sub-cultured again in medium without BPs and incubated for the desired time of the experiment. We assayed for cell proliferation using alamar blue assay and for the osteogenic differentiation using Von Kossa staining assay and calcium assay over a 2 weeks.

Results:

The data suggests that treating cells with a low single dose of drugs (100nM & 10nM) can change the cell behaviour and significantly up regulate hMSCs osteogenic differentiation and proliferation.

المؤتمر (2):

عنوان المؤتمر:

4^th International Conference Strategies in Tissue Engineering

تاريخ الإنعقاد:

10/06/2015

مكان الإنعقاد:

Wurzburg, Germany

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

In vitro Small Dose Effect of Bisphosphonates on hMSCs osteogenic response to Titanium surface

ملخص المشاركة:

Introduction:

In the last decades, titanium implant has been successfully used to replace the missing teeth. This success is mainly depending on their osseointegration; coating dental implant with deferent types of bone induced material has showed a positive effect. These materials include, bone stimulating factors, hydroxyapatite (HA) and calcium phosphate, and titanium/titanium nitride. However, human mesenchymal stem cells (hMSCs) shows regenerative properties and able to differentiate to different types of human cells such as osteoblasts. We previously reported that small dose of bisphosphonate may play an integral role of enhancing hMSCs proliferation and osteogenic differentiation. The aim of this study is to investigate wither the small dose of bisphosphonates may induce proliferation and osteogenic differentiation of hMSCs on Ti surface.  This will enhance bone quality around the implant. Also, to achieve a better osseointegration and to accelerate wound healing around the implant surface.

Materials & Methods:

In this study we investigated the small dose effect of two types of BPs (alendronate and pamidronate) on hMSCs osteogenic response to Ti surface. hMSCs were plated at a density of 1 × 104 cells/well in 1.9-cm2 wells containing MSC growth media with 10% FCS, 2 mmol L-glutamine and 100U/ml each of penicillin/streptomycin and incubated at 37ºC in humidified 5% CO2. Next day medium were changed with osteogenic media or growth media containing two different concentrations (100nM & 10nM) of the drugs. We assayed for cell proliferation using alamar blue assay and for the cells mineralisation using calcium assay and alkaline phosphates (ALP) activity. The total ECM collagen formed by cells was measured using sirocel collagen assay kit (biocolor®) according to the manufacture’s instruction.

Results:

The data suggests that treating cells with small dose (100nM & 10nM) of the drugs induce a significant stimulation of hMSCs osteogenic differentiation and cell proliferation on smooth titanium surface.

Discussion:

These experiments show that lower concentration of drugs may play an integral role of enhancing hMSCs osteogenic differentiation on titanium surface. This is due to a bisphosphonate may have a direct stimuli on osteoblasts mineralisation or bisphosphonate may enhance the wettability of titanium surface.

المؤتمر (3):

عنوان المؤتمر:

9th UK Mesenchymal Stem Cell meeting

تاريخ الإنعقاد:

03/12/2013

مكان الإنعقاد:

Manchester, UK

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Single Low dose Bisphosphonate Treatment has Long Term Effects on, and Enhances Osteogenesis in hMSCs

ملخص المشاركة:

Background:

Bisphosphonates (BPs) are analogues of pyrophosphate. They have been used to treat bone diseases characterized by excessive bone resorption such as osteoporosis and malignant bone diseases. It is well known that bisphosphonates inhibit bone resorption by interfering with osteoclasts activity.  In this study we have investigated the extended effect of a single low dose of BPs on hMSCs proliferative and osteogenic behaviour.

Methods:

In this study the effects of a single low dose of two types BPs (alendronate and pamidronate) on hMSCs behavior were investigated. hMSCs were plated at a density of 5 × 105 cells/75cm2 flasks containing MSC growth media with 10% FCS, 2 mmol L-glutamine and 100U/ml each of penicillin/streptomycin and incubated at 37ºC in humidified 5% CO2, after 24h the medium was changed with growth media containing BPs at either 100nM and 10nM and incubated for further 24h. Then, cells were then washed and trypsinized and sub-cultured again without further exposure to BPs. The cell cultures were assayed for proliferation and osteogenic differentiation using alamar blue, Von Kossa and calcium assays.

Results:

The data suggests that treating cells with a single low dose of drugs (100nM & 10nM) permanently changes the osteogenic behaviour of the hMSCs even after passaging the cells. 

Conclusions:

The enhancement of osteogenesis might point to the use of low dose BPs as an adjunct to implant placement in patients. The permanent nature of the changes suggests a possible epigenetic mechanism operating.