Recent Medical Advances

Recent medical advances have brought the possibility of growing human tissues and organs in the lab for use in patients. If this can work, it would greatly simplify transplants (eliminating most of the danger of rejection), skin grafts, knee surgery and, possibly, eye surgery. Only a few products are currently in use, such as temporary, artificial skin that can be used to help burn victims as well as lab-grown cartilage for use in knee surgery. However, there is hope in many areas such as replacement corneas, blood vessels, nerve regeneration and, perhaps, even whole organs.

There are two main possible approaches to this. One is to use human embryonic stem cells, which are derived from an embryo (and thus are surrounded by controversies such as abortion and human cloning issues) and have the potential to grow into any cell in the body given the proper environment and stimuli. In theory (but not yet in practice) an embryonic stem cell could be used to grow an entire human baby (a clone). But it can also be used to grow tissues or entire organs if the proper conditions are worked out.

Another approach involves taking cells from a person and using those already adult cells to grow tissues or organs in the lab. The advantages of this are the avoidance of immunological rejection and the avoidance of the moral issues that surround embryonic stem cells. The disadvantages are that adult cells often have a greatly reduced ability to grown and to form new tissues as compared with the embryonic stem cells. There are likely to be some kinds of tissues that simply cannot be grown from adult cells.

Either way, there are four main things, to over simplify, that are needed in order to grow a tissue or organ in the lab. First are cells that can divide and specialize into the types of cells that make up that tissue or organ. All our cells have the same genetic information, but they have activated and inactivated different parts of this genetic information. So a blood cell differs from a muscle cell which differs from a nerve cell and these cells, once developed, cannot be interconverted. An embryonic stem cell is at a very early stage of development, so if the right signals are given, it can specialize in any possible way to become part of functioning tissue. Adult cells are much more limited in their ability to do this. However, some adult cells can be used to grow other, similar cells, like skin from skin cells or cartilage from a kind of cell called a chondrocytes.

The second thing that is needed is the proper signals that will trigger a group of cells to specialize into a particular tissue that produces the proper enzymes. Some of these signals are known. Nerve Growth Factor is one signal that is needed to grow and maintain nerve cells, for example. But these signals need to be properly timed, combined with other signals and must be given in the correct amount. The slightest miscalculations can either kill the cells or produce a cancerous cell that could not be put in the body. However, in some cases the signals needed are fairly well understood and can be applied fairly easily. Again, growth of skin and cartilage have so far proven fairly easy.

The third thing is a matrix. Cells do not grow well on their own. Rather, they need something to attach to and they can sometimes be very picky about what they attach to. If they don’t properly attach, they die. On the other hand, whatever is used as a matrix for growing a tissue in the lab must not harm the patient if that tissue is transplanted. Ideally, the matrix should be able to support the cells in lab, but degrade in the patient, leaving behind the newly transplanted tissue. Several companies make biodegradable polymers (plastics) that can do just this—support growth of a thin layer of cells as it forms skin or cartilage, then degrade when it is no longer needed. This has been easy for thin tissues, but harder for more complicated, three-dimensional organs.

Which brings us to the last thing that is needed for growing a tissue or organ in the lab—organization of the cells. Cells can easily be grown in the lab as a flat layer one-cell thick. I do this all the time. However, tissues and organs require more than this. Tissues are, in essence, two-dimensional sheets of cells one- or two- cells thick. Consequently, with some care, the necessary organization can be imposed on the growing cells. However, organs are larger, three-dimensional conglomerations of cells wherein the cells form multiple layers that all must be properly coordinated. Until recently, it seemed impossible to impose such exquisite organization (note the root of the word "organization" is, indeed, "organ") from the outside. Recently, though, using branched polymer matrices rather than flat matrices, very delicate combinations of signals, and careful layering of different cell types, a supposedly functional bladder has been produced. To go beyond this to growing a more complicated organ such as a kidney, heart or lung, is still, for now, beyond our reach. Nevertheless, in only a few years, these, too, may be made in the lab and the bladder may actually be reaching the clinic.

Here are some examples of existing lab-grown tissue products as well as some products still in R+D:

Tissues that are now in use in patients: TransCyte (Advanced Tissue Sciences, La Jolla, CA.)—artificial skin grown from skin (dermal) cells on a biodegradable polymer layer. Used as a temporary skin replacement for burn patients. Carticel (Genzyme, Cambrigde MA.)—artificial cartilage grown from the patient’s own cartilage grown in a degradable matrix. Can be used to replace damaged cartilage in the knee.

Tissues successfully produced in the lab, but not yet tested in humans:

Joseph Vacanti, Harvard Medical School, has grown sections of intestine that have been successfully grafted into rats.

Francois Auger, Laval University, Quebec, has grown an artificial human cornea.

The most advanced study so far was done by Anthony Atala of Harvard Medical School who has apparently grown an entire, functioning bladder that has been successfully transplanted into dogs. This is an amazing feat which I am somewhat skeptical about. However, if true, it is a huge step forward in the field of artificially grown organs.

For further reference, there was a recent article in Science (vol. 284, no. 5413; April 16, 1999, page 422) that summarizes the current status of this field.

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Email: michad03@mcrcr.med.nyu.edu