Clinical applications of tissue engineering and cell therapy

The market for tissue engineering and cell therapy products is set to grow to nearly $32 billion by 2018. This figure includes bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration, products that often represent a combination of biotechnology, medical device and pharmaceutical technologies. The largest segment in the overall market for regenerative medicine technologies and products comprises orthopedic applications. Other key sectors are cardiac and vascular disease, neurological diseases, diabetes, inflammatory diseases and dental decay and injury.

An overview (map) of the spectrum of clinical applications in tissue engineering and cell therapy is shown below:

Source: Report #S520

Cardiology and cardiovascular medicine applications of cell therapy

Much attention has been paid to the development of cell therapies with cardiovascular applications. According to the Institute of Cardiovascular Regeneration, more than 1,500 patients with cardiovascular diseases are treated with adult progenitor cells worldwide. Much success has been achieved in this sector and cardiovascular cell therapies are increasingly becoming viable technologies.

The primary competitors in the field of tissue engineering and cell-based therapies for cardiovascular applications are shown in the exhibit below illustrating the stages in which they have cardiology/cardiovascular applications in development.

Key Competitors in Tissue Engineering and Cell Therapies for Cardiovascular Applications

Note: See specific products in development detailed in report #S520.

Source: MedMarket Diligence, LLC; Report #S520, "Tissue Engineering, Cell Therapy and Transplantation 2010."

Market Drivers: U.S. and European Cell Therapy, Tissue Engineering

Tissue engineering and cell therapy comprise a market for regenerative products that is expected to grow worldwide from $6.9 billion in 2009 to almost $32 billion by 2018. This market spans many specialties, the biggest of which is therapies for degenerative and traumatic orthopedic and spine applications. Other disorders that will benefit from cell therapies include cardiac and vascular disease, a wide range of neurological disorders, diabetes, inflammatory diseases, and dental decay and/or injury. Key factors expected to influence the market for regenerative medicine are continued political actions, government funding, clinical trials results, industry investments, and an increasing awareness among both physicians and the general public of the accessibility of cell therapies for medical applications.

There are key market drivers affecting the relative growth of cell therapy and tissue engineering in specific regions or countries. One historical driver has been the dynamics of stem cell research in the United States. The unavailability of additional stem cells due to President Bush’s Presidential Executive Order in 2001 (since rescinded in 2009 by President Obama) had the affect of decelerating the number of new embryonic stem cell research projects launched, thus postponing the optimistic timeline anticipated by some researchers. This directly delayed the commercialization of products based on embryonic stem cell research, which had the effect of dampening the overall U.S. market.  Simultaneously, this also drove increased research and development of the science (if not technologies as well) in areas outside the U.S., especially in the EU. While this distinction between the U.S. and Europe does not account for all the market size and growth differences, it is a distinct, identifiable cause.  (The U.S. also has in many respects a more mature — or at least more penetrated cell/tissue market — and the EU is simply catching up.)

Below for comparison is the relative U.S. and European share of the cell therapy and tissue engineering market in 2009 and 2019.

Source: MedMarket Diligence, LLC; Report #S520.

Cell therapy, tissue engineering and two means to one end

The subject of "tissue engineering and cell therapy" is, by some accounts, an artificial amalgam of the two separate subjects, particularly since cell therapy per se, as a result of its inextricable link to embryonic stem cells and abortion, seems to demand (at least by some) a wholly separate consideration.  From a scientific basis, of course, there is merit in the distinction, but from an industry-driven commercial consideration of diseases, disorders and trauma to be addressed — and patients served — the amalgam of cell therapy and tissue engineering is indeed warranted. For those such as we who track the developments  and markets pursued by medical technology in an era when devices compete with and/or are complementary with drugs, biotechs, biomaterials and every other technology paradigm, it is little more than an educational but largely academic exercise to make the distinction.  Medtech markets have been dramatically characterized of late, as a result of a cost- and reform-driven fixation on clinical solutions and outcomes that are achieved by any technological route. Yes, tissue engineering, biopharmaceuticals, biomaterials and other technologies are indeed distinct in nature from cell therapies in general and stem cell therapies in particular, but neither the manufacturer nor the patient particularly care about that distinction.

Below is an excerpt from Tissue Engineering, Cell Therapy & Transplantation, 2009-2018.


Cell therapy is defined as a process whereby new cells are introduced into tissue as a method of treating disease; the process may or may not include gene therapy. Forms of cell therapy can include: transplantation of autologous (from the patient) or allogeneic (from a donor) stem cells , transplantation of mature, functional cells, application of modified human cells used to produce a needed substance, xenotransplantation of non-human cells used to produce a needed substance, and transplantation of transdifferentiated cells derived from the patient’s differentiated cells.

Once considered a segment of biomaterial technologies, tissue engineering has evolved into its own category and now comprises a combination of cells, engineering and suitable biochemical and physiochemical factors to improve or replace biological functions. These include ways to repair or replace human tissue with applications in nearly every medical specialty. Regenerative medicine is often synonymous with tissue engineering but usually focuses on the use of stem cells.

For the purposes of definition, tissue engineering and cell therapy comprise bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration. These often comprise a combination of biotechnology, medical device and pharmaceutical technologies.

Researchers have been examining tissue engineering and cell therapy for roughly 30 years. While some products in some specialties (such as wound care) have reached market, many others are still in research and development stages. In recent years, large pharmaceutical and medical device companies have provided funding for smaller biotech companies in the hopes that some of these products and therapies will achieve a highly profitable, commercial status. In addition, some companies have been acquired by larger medical device and pharmaceutical companies looking to bring these technologies under their corporate umbrellas. Many of the remaining smaller companies received millions of privately funded dollars per year in research and development. In many cases it takes at least ten years to bring a product to the point where human clinical trials may be conducted. Because of the large amounts of capital to achieve this, several companies have presented promising technologies only to close their doors and/or sell the technology to a larger company due to lack of funds.

The goal of stem cell research is to develop therapies to treat human disease through methods other than medication. Key aspects of this research are to examine basic mechanisms of the cell cycle (including the expression of genes during the formation of embryos) as well as specialization and differentiation into human tissue, how and when the differentiation takes place and how differentiated cells may be coaxed to differentiate into a specific type of cell. In the differentiation process, stem cells are signaled to become a specific, specialized type of cell when internal signals controlled by a cell’s genes are interspersed across long strands of DNA and carry coded instructions for all the structures and functions of a cell. In addition, cell differentiation may be caused externally by use of chemicals secreted by other cells, physical contact with neighboring cells and certain molecules in the microenvironment.

The end goal of stem cell research is to develop therapies that will allow the repair or reversal of diseases that previously were largely untreatable or incurable.. These therapies include treatment of neurological conditions such as Alzheimer’s and Parkinson’s, repair or replacement of damaged organs such as the heart or liver, the growth of implants from autologous cells, and even regeneration of lost digits or limbs.

In a developing human embryo, a specific layer of cells normally become precursor cells to cells found only in the central nervous system or the digestive system or the skin, depending on the cell layer and the elements of the embryo that direct cell differentiation. Once differentiated, many of these cells can only become one kind of cell. However, researchers have discovered that adult body cells exist that are either stem cells or can be coaxed to become stem cells that have the ability to become virtually any type of human cell, thus paving the way to engineer adult stem cell that can bring about repair or regeneration of tissues or the reversal of previously incurable diseases.

Another unique characteristic of stem cells is that they are capable of self-division and self-renewal over long periods of time. Unlike muscle, blood or nerve cells, stem cells can proliferate many times. When exposed to ideal conditions in the laboratory, a relatively small sample of stem cells can eventually yield millions of cells.

There are five primary types of stem cells: totipotent early embryonic cells (which can differentiate into any kind of human cell); pluripotent blastocyst embryonic stem cells, which are found in an embryo seven days after fertilization and can become almost any kind of cell in the body; fetal stem cells, which appear after the eighth week of development; multipotent umbilical cord stem cells, which can only differentiate into a limited number of cell types; and unspecialized adult stem cells, which exist in already developed tissue (commonly nerves, blood, skin, bone and muscle) of any person after birth.

Source: MedMarket Diligence, LLC; Report #S520

Medical Technology Market Reports from MedMarket Diligence, LLC

The following reports are recent titles from MedMarket Diligence, LLC:

Tissue Engineering & Cell Therapy Worldwide Market, 2009-2018

Wound Management Worldwide Market, 2008-2017 

Drug-Eluting, Bare Metal and Other Coronary Stents, Worldwide Market, 2008-2017

The following reports are slated for publication in May and June:

Ablation Technologies Worldwide Market 2009-2018 

Diabetes Management: Products, Technologies, Markets and Opportunities Worldwide 2009-2018

Technology migration in medtech markets

Western markets, including the U.S. and Europe, tend to drive the formation of new medical technology markets, which then evolve and migrate to Asia/Pacific and the rest of the world.  While this is not always the case (a notable exception is the technology and market development of fibrin and other blood-based tissue sealants technologies, which substantially took hold in Japan first), it is often the case due to the level of innovation in these markets, available capital for investment and, in no small part (and to the ire of the cost conscious) the high percent of gross domestic product spent on healthcare, especially in the U.S.

One of the most well established markets for cell therapy and tissue engineering products, and second only to orthopedics, is in the area of skin or integumentary applications — treatment of burns, diabetic and venous ulcers and plastic and reconstructive surgery.  As an example of the trend of U.S. markets driving innovation, the market for cell/tissue products in skin applications has been dominated by the U.S., and the recent past trend in reported revenues geographically, which is certainly going to continue, is that the U.S. will represent a progressively smaller share of this global market.

Source: MedMarket Diligence, LLC; Report #S520.

Neurological applications of products in cellular therapy and preclinical, clinical and approved stages

Cellular therapeutics with neurology applications currently encompass the entire range of development from preclinicals to approved, commercially available products in use.

See the specific selected neurology cell therapy products on the market or in development by companies in the market:

  • Personalized stem cell therapies for tissue regeneration
  • Cell treatment for amyotropic lateral sclerosis
  • Biopharmaceutical for stroke
  • MultiStem for attentional/cognitive areas; MultiStem Stroke
  • Cellular (embrionic stem cell) implants for the regeneration of damaged or sick neural tissue
  • Stem cells for neurodegenerative diseases
  • Autologous cell-based therapies for neurosurgical applications
  • Neural progenitor cells
  • Biopharmaceuticals for chronic regenerative disorders, including spinal cord injury (glial cells)
  • Biotech diagnostic assays for neurodegeneration and other applications
  • Regenerative implants for neurosurgical applications
  • Neurotrophin cellular therapy for Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and stroke
  • Stem cell-based therapies for neurological and other applications
  • Human neural stem cell transplantation
  • Neural stem therapies for patients with neurological diseases such as Parkinson’s, Alzheimer's, epilepsy, spinal cord injury, stroke and multiple sclerosis and amyotropic lateral sclerosis
  • Biotherapeutics for amyotropic lateral sclerosis and Parkinson’s
  • Bioregeneration matrix
  • Stem cell therapies for neurological applications (multiple sclerosis, stroke)
  • Bioresorbable nerve guide
  • Cellular therapy for spinal cord injury
  • Neurological cell growth and function
  • Stem cell therapy for disabled stroke victims
  • Plans to develop and commercialize products for Parkinson's, spinal cord injury, and other diseases
  • Stem cell-based biopharm for neurodegenerative and other diseases
  • Cell-based technologies for CNS and liverHuCNS-SC (purified human neural stem cells) for neurodegenerative disorders
  • Therapeutics for neurodegenerative diseases
  • Dura substitute for repair of cranial dura mater, spinal dura mater (marketed by Medtronic)
  • Biopharmaceutical for Alzheimer's
  • Stem cells created from adult cells (retrodifferentiation technology) possibly to be developed for spinal cord injury applications

The global market for neurological applications of cellular and tissue engineered therapeutic products is currently under $300 million, but is on pace to near $1 billion by 2018. (See MedMarket Diligence report #S520.)

U.S., Europe lead cell/tissue therapeutics markets

Worldwide sales of cell therapy and tissue engineering products eclipsed $6.9 billion in 2009 on pace to reach $32 billion by 2018.  This figure includes bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration, products that often represent a combination of biotechnology, medical device and pharmaceutical technologies. The largest segment in the overall market for regenerative medicine technologies and products comprises orthopedic applications. Other key sectors are cardiac and vascular disease, neurological diseases, diabetes, inflammatory diseases and dental decay and injury. 

Factors that are expected to influence this market and its explosive growth include political forces, government funding, clinical trial results, industry investments (or lack thereof), and an increasing awareness among both physicians and the general public of the accessibility of cell therapies for medical applications. Specifically, President Obama’s repeal of a Presidential Executive Order has given researchers sponsored with Federal funding increased access to additional lines of embryonic stem cells. This is expected to result in an increase in the number of research projects being conducted and thus possibly hasten the commercialization of certain products.

Another factor that has influenced the advancement of regenerative technologies is found in China, where the Chinese government has encouraged and sponsored cutting-edge (and some have complained ethically questionable) research. While China’s Ministry of Health has since (in May 2009) established a policy requiring proof of safety and efficacy studies for all gene and stem cell therapies, the fact remains that this research in China has spurred the advancement of (or at least awareness of) newer applications and capabilities of gene and stem cell therapy in medicine.

Meanwhile, stricter regulations in other areas of Asia (particularly Japan) will serve to temper the overall growth of commercialized tissue and cell therapy–based products in that region. Nonetheless, the growth rate in the Asia/Pacific region is expected to be a healthy 20% (CAGR 2009–2018), as shown below.

 

 

Source: Report #S520, MedMarket Diligence, LLC

Regenerative medicine promises realized

The first annual Translational Regenerative Medicine Forum that was held April 6-10, 2010, and sponsored by the Regenerative Medicine Foundation highlighted the future promise and needs in this field encompassing succinctly:

  • replacement tissues and organs
  • cell therapies to restore function

Other issues addressed include the perennial discussion of policy, funding and the challenges of stem cells, both for embryonic and pluripotent stem cells.

The specific applications discussed at the forum included:

  • regeneration of the pancreas' islet cells to restore insulin production for diabetics
  • application of regenerative medicine to treatment of battlefield injuries
  • cell applications to degenerative retinal disease
  • outpatient procedure to regenerate disc tissue
  • injectable therapy to treat heart tissue after heart attack

Given the thrust of the forum, as a forward-looking event that looked at challenges of the field, the promise of new developments and the needs of regenerative medicine, there is a tendency to underestimate the extent the current successful status of regenerative medicine.  (Of course, the forum did include presentations by 18 regenerative medicine technologies seeking potential investment from VC groups like DeNovo Ventures, Excel Venture Management, InterSouth Partners, Livingston Securities, Proteus Ventures, and Quaker BioVentures.)  As much as the forum focused on the great potential of regenerative medicine market and the challenges it faces, one might say that the forum could not possibly represent the extent to which regenerative medicine promises have already been realized.  Here are some examples:

  • The global market for cell therapy and tissue engineering technologies is currently $6.9 billion per year, growing at an aggregate 18%.
  • The global market includes $4.35 billion from orthopedics and musculoskeletal applications, $679 million from skin/integumentary applications, $374 million from dental/oral surgery applications and $468 million from cardiology applications.
  • There are currently hundreds of active companies in this global market.
  • The top five major medtech companies account for a total of $4.3 billion in regenerative medicine revenues annually.

Indeed, the discussion of promise in the field of regenerative medicine — from the standpoint of patients treated, clinical problems solved, future market realized and all of the above — remains huge and, to a great and practical extent, very much within reach.  By our projections, the advances in approved products, clinical applications and resulting market for regenerative medicine will reach $32 billion annually by 2018.

For further detail, see Report #S520.