REPROCELL

REPROCELL is the exclusive provider of the Stemgent® StemRNA™ 3rd Gen reprogramming
technology — the most rapid, robust, and clinically relevant integration-free method on the market.
We offers custom iPSC production services to clients in industry and academia with over 15 years’ experience as leaders in stem cell research. The third generation RNA technology is faster, more stable and footprint-free, allowing REPROCELL to deliver iPSCs in around half the time of its competitors.

Global custom service and research labs in America, Europe and Asia:

• Fresh, normal or diseased tissue available through our custom collection network
• Establishment of patient-derived primary somatic cell lines as part of the standard service
• Reprogramming of multiple human and non-human cell types
• Cryopreserved patient-derived primary cells and iPSCs expanded and provided
• Management of projects based on milestone achievements for flexible project customization and fair value

Biopta’s human tissue models provide an excellent first look at how your test compound will perform far in advance of being in the clinic.

Our models can provide invaluable human efficacy data while your compounds are still in pre-clinical development; greatly increasing the predictability of your drug development, meaning ‘go’ or ‘no-go’ decisions can be made with confidence prior to expensive clinical studies.

Both healthy and diseased tissues are often freely available and enable researchers to make detailed ‘phase 0’ comparisons in select patient populations without the associated large costs. Human efficacy data adds significant value for investors and can be extremely useful when looking for expected secondary applications or repositioning of current compounds.

Biopta offers a range of validated assays across all therapeutic areas as well as a dedicated assay development team who are able to provide customised assays to meet your specific needs.The flow chart below shows a typical project at Biopta- note that the tissue type and endpoint is highly flexible, here, an example is shown using small blood vessels dissected from subcutaneous adipose tissues.

Efficacy data in living human tissues is a powerful method to demonstrate the value of your compounds:

• For investors- confidence increased by early demonstration of human efficacy in the target patient group
  
• Adds commercial value- reduces risk of phase II failure, which adds early stage value to the compounds
  
• De-risks development by selecting compounds with demonstrable human efficacy
  

Contact Biopta today to design a protocol that will demonstrate the efficacy of your compounds in human fresh tissues.

Through an extensive array of ex vivo human tissue assays, Biopta is able to provide invaluable human safety data for your compound early in the development cycle.

The benefits of undertaking safety testing in human tissues are many. When carried out in conjunction with the ICH S7A core battery, our data can provide an unparalleled indication of clinical safety and even reduce the number of animals required for in vivo experimentation. More importantly though, our data can help reduce the number of late stage failures as ‘go’ or ‘no go’ decisions can be made with confidence based on human responses. In addition to the positive effect on cost and time to clinic, human safety data adds significant value for investors and potential partners.

Routine safety assays conducted by Biopta include:

Ion channel function in isolated healthy human gastrointestinal mucosa

The intestines are essential for the digestion of foor and the absorption of fluid and electrolytes. Changes in the anatomy or function of the intestines can lead to disorders such as Irritable Bowel Syndrome (IBS), Crohns, Ulcerative Colitis and diarrhoea.

Ion channel function in healthy human tracheal mucosa

The airways of the respiratory tract offer resistance to the flow of air during inhalation and expiration. Any alterations to the airways (for example contractile state, increased mucus or inflammation of the airways) can affect airflow and gas exchange.

Assay Type Reference Number Assay Description
Adrenoceptors B062 This assay asseses whether a test compound causes a change in short circuit current across healthy human tracheal mucosa with isoprenaline as a reference compound.
Sodium channels B063 This assay asseses whether a test compound causes a change in short circuit current across healthy human tracheal mucosa with amiloride as a reference compound.

The intestines are essential for the digestion of food and the absorption of fluid and electrolytes. changes in the anatomy or function of the intestines can lead to disorders such as Irritable Bowel Syndrome (IBS), Crohns, Ulcerative Colitis and diarrhoea.

Relaxation in Human Bladder

The primary function of the bladder is the storage of urine before micturition. The contraction and relaxation of the smooth muscle controls the emptying and filling of the bladder. Alterations to the anatomy of the bladder can affect filling and emptying, causing disorders such as incontinence and bladder hypertrophy.

** Relaxation in human uterus**

The uterus is one of the female reproductive organs. The main functions of the uterus are to provide a suitable site for an implanting blastocyst, to expand with the growing foetus and to contract strongly to expel the foetus. Alterations to the anatomy of the uterus may adversely affect its functionality.

Assay Type Reference Number Assay Description
Nitric Oxide Donor B081 This assay assesses whether test articles cause a reduction in spontaneous activity in isolated human uterine tissue, with sodium nitroprusside as a reference compound.
Adrenoceptor - Isoprenaline B082 This assay assesses whether test articles cause a reduction in spontaneous activity in isolated human uterine tissue, with isoprenaline as a reference compound.
Calcium Channels B083 This assay assesses whether test articles cause a reduction in spontaneous activity in isolated human uterine tissue, with isradipine as a reference compound.

Relaxation in human ureter

The ureter connects the kidneys to the urinary bladder. The ureter has a smooth muscle layer which propels urine to the bladder, via peristalsis, a phenomenon that can be observed in vitro.

Assay Type Reference Number Assay Description
Adrenoceptor - Isoprenaline B071 This assay assesses whether test carticles cause relaxation in isolated human ureter, with isoprenaline as a reference compound.

Bronchodilatation in secondary COPD human airways

The airways of the respiratory tract offer resistance to the flow of air during inhalation and expiration. Any alterations to the airways (for example contractile state, increased mucus or inflammation of the airways) can affect airflow. Chronic Obstructive Pulmonary Disease (COPD) is the term given to a collection of airway disorders including bronchitis and emphysema. COPD is generally caused by an obstruction to airflow caused by a narrowing of the airways. Over time, the damage to the airways such as scarring, increased mucus and loss of elasticity also contribute to the restricted airflow and increased workload for the respiratory muscles.

Bronchodilatation in secondary healthy human airways

The airways of the respiratory tract offer resistance to the flow of air during inhalation and expiration. Any alterations to the airways (for example contractile state, increased mucus or inflammation of the airways) can affect airflow and gas exchange.

Assay Type Reference Number Assay Description
Adrenoceptor - Isoprenaline B052 This assay assesses whether test compounds cause bronchodilation in healthy human airways with isoprenaline as a reference compound.
VIP & PACAP receptors B098 The experiment assesses whether test articles cause bronchodilatation in isolated healthy human secondary airways with Vasoactive Intestinal Polypeptide (VIP) as a reference compound.

** Bronchodilatation in tertiary or lower human airways**

The airways of the respiratory tract offer resistance to the flow of air during inhalation and expiration. Any alterations to the airways (for example contractile state, increased mucus or inflammation of the airways) can affect airflow and gas exchange.

Assay Type Reference Number Assay Description
Adrenoceptors - Formoterol B065 This assay assesses whether test compounds cause bronchodilation in human airways with formoterol as a reference compound.
Adrenoceptors - Salbutamol B066 This assay assesses whether test compounds cause bronchodilation in human airways with salbutamol as a reference compound.
Adrenoceptor - Formoterol B067 This assay assesses whether test compounds cause bronchodilation in asthmatic human airways with formoterol as a reference compound.
Adrenoceptor - Salbutamol B068 This assay assesses whether test compounds cause bronchodilation in asthmatic human airways with salbutamol as a reference compound.
Adrenoceptor - Salmeterol B069 This assay assesses whether test compounds cause bronchodilation in asthmatic human airways with salmeterol as a reference compound.

The airways of the respiratory tract offer resistance to the flow of air during inhalation and expiration. Any alterations to the airways (for example contractile state, increased mucus or inflammation of the airways) can affect airflow. Asthma involves both large and small airways and is characterised by inflammation, predominantly mediated by lymphocytes and eosinophils, in the airways and reversible smooth muscle constriction (bronchospasm).

Bronchoconstriction in denuded secondary healthy human airways

The airways of the respiratory tract offer resistance to the flow of air during inhalation and expiration. Any alterations to the airways (for example contractile state, increased mucus or inflammation of the airways) can affect airflow and gas exchange.

Assay Type Reference Number Assay Description
Acetylcholine receptor B060 This assay assesses whether test compounds cause bronchoconstriction in denuded human airways with carbachol as a reference compound.
Histamine receptor B061 This assay assesses whether test compounds cause bronchoconstriction in denuded human airways with histamine as a reference compound.

Bronchoconstriction in tertiary or lower healthy human airways

The airways of the respiratory tract offer resistance to the flow of air during inhalation and expiration. Any alterations to the airways (for example contractile state, increased mucus or inflammation of the airways) can affect airflow and gas exchange.

Assay Type Reference Number Assay Description
Prostanoid receptor B055 This assay assesses whether test compounds cause bronchoconstriction in healthy human airways with U46619 as a reference compound.
Adrenoceptor - Salbutamol B056 This assay assesses whether test compounds cause bronchodilation in healthy human airways with salbutamol as a reference compound.
Acetylcholine receptor B057 This assay assesses whether test compounds cause bronchoconstriction in healthy human airways with acetylcholine as a reference compound.
Adrenoceptor - Isoprenaline B058 This assay assesses whether test compounds cause bronchodilation in healthy human airways with isoprenaline as a reference compound.
lopoxin, oxoeiconsanoid and resolvin E1 B099 The experiment assesses whether test articles cause bronchoconstriction in isolated healthy human tertiary or lower airways, with Leukotriene D4 (LTD4) as a reference compound.

Vasodilatation in human skeletal muscle arteries

The skeletal muscle vasculature is the largest vascular bed in the body, therefore changes in skeletal blood flow and pressure can directly affect peripheral vascular resistance and arterial blood pressure.

Vasodilatation in ischaemic human subcutaneous resistance arteries

Resistance arteries are involved in regulating organ specific blood flow and offer the greatest resistance to blood flowing into tissues. Resistance arteries therefore play an important role in the regulation of peripheral vascular resistance and arterial blood pressure.

Vasodilatation in human subcutaneous resistance arteries

Resistance arteries are involved in regulating organ-specific blood flow throughout the body and offer the greatest resistance to blood flowing into tissues. Resistance arteries therefore play an important role in the regulation of arterial blood pressure. Ischaemia is a period of time with restricted blood flow, which can potentially lead to irreversible tissue. Ischaeamia can be caused by a variety of disorders such as atherosclerosis, tachycardia or hypotension. Biopta can source arteries from tissues that have been exposed to these conditions.

Vasodilatation in human pre-eclamptic chorionic plate arteries

Chorionic plate arteries supply blood and nutrients to the growing foetus making them essential for healthy development. Any disruption to blood flow can cause adverse effects to the foetus. Pre-eclampsia is characterised by reduced maternal-foetal blood flow, causing potential health risks to both mother and foetus.

Vasodilatation in human chorionic plate arteries

Chorionic plate arteries supply blood and nutrients to the growing foetus making them essential for healthy development. Any disruption to blood flow can cause adverse effects to the foetus.

Vasoconstriction in atherosclerotic human subcutaneous resistance arteries

Resistance arteries are involved in regulating organ-specific blood flow throughout the body and offer the greatest resistance to blood flowing into tissues. Resistance arteries therefore play an important role in the regulation of arterial blood pressure. Atherosclerosis is the formation of fatty lesions or fibrous plaques in the smooth muscle of arteries. This causes a narrowing of the vessels, an increase in blood pressure and an increased risk of myocardial infarction and stroke.

Vasoconstriction in human coronary arteries

Coronary arteries are the blood supply to the myocardium. Changes in blood flow and vascular tone can greatly affect cardiac function; even a brief reduction in coronary blood flow can induce dysfunction of the heart.

Assay Type Reference Number Assay Description
5-HT receptor - 5-HT B003 The experiment assesses whether test articles cause vasoconstriction in human coronary arteries with 5-HT as a reference compound.
Opioid and opioid-like receptors B004 The experiment assesses whether test articles cause vasoconstriction in human coronary arteries with mephedrone as a reference compound.
Angiotensin receptor B007 The experiment assesses whether test articles cause vasoconstriction in human coronary artries with angiotensin II as a reference compound.
Vasopressin & oxytocin receptors B008 The experiment assesses whether test articles cause vasoconstriction in human coronary arteries with 8-arginine vasopressin as a reference compound.
5-HT receptor - Sumatriptan B028 The experiment assess whether test articles cause vasoconstriction in human coronary arteries with sumatriptan as a reference compound.

Vasoconstriction in human saphenous vein

The venous system is involved in returning blood back to the heart from tissues. The venous system can contain up to 70% of blood in the circulation. This reservoir of blood allows veins to adjust the volume of blood returning to the heart at any one time, therefore altering cardiac output.

Assay Type Reference Number Assay Description
5-HT receptor B023 The experiment assesses whether test articles cause vasoconstriction in human saphenous vein with sumatriptan as a reference compound.

Vasoconstriction in denuded human coronary arteries

Coronary arteries are the blood supply to the myocardium. Changes in blood flow and vascular tone can greatly affect cardiac function; even a brief reduction in coronary blood flow can induce dysfunction of the heart.

Assay Type Reference Number Assay Description
5-HT receptor B030 The experiment assesses whether test articles cause vasoconstriction in denuded human coronary arteries with 5-HT as a reference compound.

Resistance arteries are involved in regulating organ-specific blood flow and offer the greatest resistance to blood flowing into tissues. Resistance arteries therefore play an important role in the regulation of peripheral vascular resistance and arterial blood pressure.

Biopta is able to provide information on the absorption and metabolism characteristics of your compounds in ex vivo human respiratory, skin and gastrointestinal tissues by employing Ussing Chambers to mount intact sheets of human epithelium that retain all the relevant characteristics to model passive and active transport of substances.

The Ussing chamber allows measurement of short-circuit current through intact membranes, providing information on ion channel activity. Moreover, as the tissue is fresh and functional, transport and metabolism across various regions of the GI tract or trachea/lung can be estimated and compared with data from animal systems or CaCo-2 models. For example, you might wish to compare the absorption of your compound in the stomach, small intestine and large intestine.

Biopta's test systems are the only available method to predict the actual absorption and metabolism in intact fresh human tissues, the closest method to testing in the clinic.

Biopta's system is the only method that allows measurements of drug absorption, transporter effects and metabolism in the one experiment, making it more cost-efficient than individual assays. Moreover by using native human tissues it is the closest possible model of humans. We have industry's only database of human tissue assays.

Biopta will create a protocol customised to meet your ADME needs, allowing confidence that your compounds will be successful in patients.

Contact us today to discuss how to add commercial value through human data.

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