Monday, November 04, 2019

Scientists 3D-print living skin with blood vessels

Scientists in the US have created 3D-printed skin complete with blood vessels, an advancement which they hope could be a significant step toward creating grafts that are more like the skin our bodies naturally produce. 

The team of researchers at Rensselaer Polytechnic Institute in New York and Yale School of Medicine combined cells found in human blood vessels with other ingredients, including animal collagen, and printed a skin-like material.

After a few weeks, the cells started to form into vasculature (the arrangement of blood vessels in an organ or part), after which the skin was transplanted onto a mouse. Following this procedure, the team found the skin connected with the animal’s vessels.

“Right now, whatever is available as a clinical product is more like a fancy Band-Aid,” said Pankaj Karande, an associate professor of chemical and biological engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer.

“It provides some accelerated wound healing, but eventually it just falls off. It never really integrates with the host cells,” he added.

A significant barrier to the integration between cells has been the absence of a functioning vascular system in the skin grafts. For several years, Karande and his team have been working to tackle this challenge.

In one of the team’s first papers on the subject, the researchers found they could take two types of living human cells, make them into ‘bio-inks’ and print them into a skin-like structure.

Since then, he and his team have been working with researchers from Yale School of Medicine to incorporate vasculature to these cells.

In their latest study, the researchers demonstrated that if they add key elements – including human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells – with animal collagen and other structural cells typically found in a skin graft, the cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks.

Karande said: “As engineers working to recreate biology, we’ve always appreciated and been aware of the fact that biology is far more complex than the simple systems we make in the lab.

“We were pleasantly surprised to find that, once we start approaching that complexity, biology takes over and starts getting closer and closer to what exists in nature.”

Once the Yale team grafted it onto a special type of mouse, the vessels from the skin printed by the Rensselaer team began to communicate and connect with the mouse’s own vessels.

“That’s extremely important because we know there is actually a transfer of blood and nutrients to the graft which is keeping the graft alive,” Karande added.

In order to make this process usable at a clinical level, however, the researchers would need to be able to edit the donor cells using CRISPR (gene editing) technology to ensure that the vessels can integrate and be accepted by the patient’s body.

“We are still not at that step, but we are one step closer,” Karande said.

“This significant development highlights the vast potential of 3D bioprinting in precision medicine, where solutions can be tailored to specific situations and eventually to individuals,” said Deepak Vashishth, the director of CBIS. “This is a perfect example of how engineers at Rensselaer are solving challenges related to human health.”

Karande added that more work will need to be done to address the challenges associated with burn patients, which include the loss of nerve and vascular endings.

However, the grafts his team have created bring researchers closer to helping people with more discrete issues such as diabetic or pressure ulcers.

“For those patients, these would be perfect, because ulcers usually appear at distinct locations on the body and can be addressed with smaller pieces of skin,” Karande explained. “Wound healing typically takes longer in diabetic patients and this could also help to accelerate that process.”

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Friday, March 09, 2018

Artificial intelligence methods used for developing precision cancer medicine

A patient's own molecular data can be used to identify, with the use of artificial intelligence methods, the best combinatorial multi-drug therapy for that patient. Network modeling plays a major role in this line of work.


The concept of this project is that a patient's own molecular data can be used to identify, with the use of artificial intelligence methods, the best combinatorial multi-drug therapy for that patient. Network modeling plays a major role in this line of work, integrating genome-scale patient data into detailed interaction networks, that can be analyzed by Combio's recently developed algorithms to identify combinations of drugs and inhibitors that are likely to be therapeutically effective. The project focuses on individual patients with the goal to dynamically adapt their therapeutical strategies to avoid the onset of drug resistance.


In addition to the Computational Biomodeling Laboratory, the project involves 4 Finnish companies (Misvik Biology, Medi Sapiens, Orion Pharma, Euformatics). The renowned US-based Moffitt Cancer Research Centre in Tampa, Florida is a new key contributor to the project, with large patient data sets and extensive validation capabilities. The infrastructure available at the Moffitt Cancer Research Centre gives access to extensive patient samples, gene editing techniques, genome-scale analysis, and translational studies. This gives a very short cycle between computational predictions and experimental validation.
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Sunday, July 17, 2016

Precision Medicine - A breakthrough in cancer treatment

Dr. Meenu Walia, Director of Max Oncology Centre at the Max Hospital, Patparganj, is the first DNB medical oncologist of India who has been the Principal Investigator of several Multi-Centric International Clinical Research trials where newer options for Cancer treatment are evaluated. ETHealthworld talks to Dr Walia to know more about the role of precision medicine in cancer treatment.

Why is precision medicine so important?

Precision medicine is a medical breakthrough which promises to open up great opportunities in personalised cancer care. According to recent medical research, everyone has unique genetic composition, as well as personal and molecular characteristics. Every human being leads a unique life in terms of environmental conditions and lifestyle. This is an important finding for a complex disease, such as cancer. Cancer is caused when the DNA composition in the cells suffers damage resulting in uncontrolled abnormal growth of cells known as cancerous cells. Factors that make precision medicine one of the most sought after medical approach are:

Its effectiveness and efficiency
Fewer side effects
Targeted treatment

What wonders can precision medicine work in cancer treatment?

According to a study by the NCBI, the total number of cancer cases in India is expected to cross 1,14,8757 by the year 2020.1 One way of looking at this figure is that there are 1,14,8757 unique cancer cases expected in the year 2020.

Precision medicine has finally come as an answer to one of the most challenging questions in cancer treatment. Scientists were puzzled as to why some cancer patients do not respond well to the best of the standard cancer treatment, while others do. The number of cancer cases is expected to rise considerably in the next five years in India. Precision medicine is certainly going to change the way cancer has been treated till date. It would give us more insights into cancer and hopefully would lead to better and effective outcomes. It also holds lots of promising new advancements in cancer care and early diagnosis.

How is precision medicine personalised?

Personalisation may take different forms when it comes to cancer. These include:
Cancer testing to determine whether a particular treatment would be effective in a particular case
Genetic profiling of the patient to understand whether he/she can handle a particular medicine or therapy
Profiling the genetical composition of a person with regard to genetic mutation to determine the degree of cancer risk

What is the current status of precision medicine in India?

Precision medicine in India is believed to be in its infancy. Although in its early stages, it still offers huge potential in terms of research and development and their application. Precision medicine has generated tremendous interest in the Indian medical fraternity. It has forced most of the industry players to rethink on their future strategies. India with its diversity and large population base would be an ideal testing ground for precision medicine. Patient information is the focal point of any precision medicine research; therefore it would need proactive involvement of patients.

What is the global scenario?

The scientist community has hailed precision medicine and is eager to adopt it as the latest medical advancement. The medical fraternity across the world has been working relentlessly in making precision medicine more affordable. Still, precision medicine has a long way to go before it is within the reach of a common man in India. Nevertheless, it has come as a ray of hope for many.

What does precision medicine mean for the medical fraternity and the stakeholders?

The recent announcement by the US government backing the precision medicine research and its clinical application has created a stir in the healthcare industry worldwide. Precision medicine has become the driving force for various stakeholders of the industry. Precision medicine based treatment approach has led almost all major pharmaceutical companies to conduct researches into it, to get the first mover advantage. Oncology, followed by neurology and cardiology branch of medical sciences are the ones, which would be getting the maximum benefit out of these research and development. The other medical science branches are would soon follow suit.

What is the scope for precision medicine in India?

Precision medicine is still in its early stage in India. However, it has opened up a novel approach to treat a deadly disease like cancer. It offers high potential and is much-needed in the Indian healthcare scenario, as the Indian health sector is overburdened with the ever-increasing epidemic ready to engulf the Indian population.

Most of the doctors agree on the fact that precision medicine is the next thing in medical practice and are keeping them abreast with the recent developments in this field. There would be major collaboration among the scientists, medical practitioners, IT, insurance and pharmaceuticals community to put in their best to tap the potential that precision medicine has on offer.


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Monday, March 28, 2016

Oncologists take to precision medicine

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOUR PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.



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 When Anant's colon cancer relapsed early this year and chemotherapy was recommended, he requested for treatment with the least side-effects. His doctor sent his blood sample for a specific chemotherapy he had in mind. The doctor is thanking his foresight after the test results showed that Anant severely lacked an enzyme needed to process or metabolize that particular chemotherapy drug. Had he been administered it, Anant may have had life-threatening side effects.

Such personalized or precision cancer care is about analysing a patient's tumour to determine what combination of drugs will work best. With this level of specificity also comes a greater potential to decrease toxic side effects, say experts.

"The study of analysing blood to test for genetic variants of enzymes that help process different types of drugs is called pharmacogenomics. Each individual processes a drug differently depending on his or her unique genetic make-up. What happened in Anant's case is one of the examples of precision medicine," medical oncologist Shona Nag said.

Precision cancer medicine is used to describe treatments which are given to patients with similar tumours, but tailored according to their unique genetic, physical and psycho social characteristics.

Two women, Arpita and Anjali, have the same stage and type of breast cancer and both required chemotherapy. "Arpita had severe diabetes and Anjali did not. The specialist chose different chemotherapies for each of them, making sure that Arpita did not suffer from side effects. Her treatment was personalized according to her special needs," said Nag.

Precision medicine is driven by newer diagnostic and therapeutic technologies and relies on the advances made by genetic sequencing of tumours and blood to precisely identify which treatment should be used and when.

"It helps choose the correct treatment for a particular tumour sub-type," Nag said. She heads the medical oncology department at Jehangir Hospital and is trustee of Nag Foundation that works in cancer care, research and education.

Software professional Rajat was recently diagnosed with advanced stage four lung cancer.

Ten years ago, despite undergoing chemotherapy sessions, he would not have survived for more than 6-8 months. Rajat was put through a biopsy and one of the lungs showed a type of cancer called adenocarcinoma. The tumour is subjected to genetic testing for abnormal `driver mutations'.

"These are genetic changes which actually drive the growth of the tumour," Nag said. Rajat was put on a new oral targeted therapy directed to stem this mutation. Since he responded well to treatment, it has significantly improved his chances of survival.


 "Lung tumours can be sub-typed into distinct groups based on genetic profiles.There are specific non-chemotherapeutic drugs which treat these tumours. These are all examples of precision medicine," Nag said Precision medicine helps avoid unnecessary chemotherapy as well. Rashmi, a 43 year-old homemaker, was recently operated for breast cancer and the tumour which was removed, was a mild sub-type.
Her surgeon recommended that she see a medical oncologist for chemotherapy and when Rashmi explained her reservations to her oncologist, a genetic test called endopredict was done which characterized her tumour as low risk and she could safely avoid chemotherapy and take hormone tablets.

"Our treatment choices are now very precise with genetic tests on the tumour and especially in breast cancer it is now possible to avoid unnecessary treatments which may not benefit the patient at all," breast surgeon Anupama Mane said.


Success stories abound, but medical science has not achieved breakthroughs in treating many tumours.

Genetic sequencing and genetic profiling have identified many mutations in tumours. "Often, we don't know if these mutations are important enough to drive the tumour growth and spread. We can find the driver mutations, but there may not be effective drugs. So there are many caveats in precision medicine. It is the future of cancer care and it can change the way we treat cancer," Nag said.

Molecular geneticist Nikhil Phadke said, "We see patients with blood, breast, lung, and colon cancer being referred for genetic testing on a routine basis. This testing is either for predictive purposes or for precision medicine guidance, where genetic tests are increasingly being used to determine which drug may be used for treatment."

In some cases, more sophisticated genetic tests are required to ascertain why the patient is no longer responding well to the first choice drug, he added. "We have had more than a few cases where patients respond well after being put on a new drug based on the results of these tests," Phadke said.

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