Orthopaedic tissues transplanted into humans are dead.
That’s right: Other than hearts, livers and kidneys that must be kept alive for immediate transplantation, any tissue removed from a donor or a cadaver that is frozen, washed, sterilized and finally delivered to a surgeon is dead. From there, it may be used in new ACL grafts, meniscus replacements, rotator cuff patches, tendons for the hands and feet … the list goes on.
The surgeon relies on the patient’s healing ability to recognize and revive the dead donor graft. The body does this by sending scavenger cells that open up pores for the new blood vessels to bore into, lacing new blood vessels into the tissue, and finally sending specialized cells that lay down new collagen and restore the graft to life. In ligaments, this wonderful tissue regeneration process is called “ligamentization,” in other tissues it’s called “remodeling.”
But the process of remodeling takes time. And during that period of restoration, the tissue is at its weakest stage. A new injury doesn’t need to be very forceful to tear the healing tissue. And any illness might slow down the process. An early return to sports might put too much stress on the graft, leading to stretching — or in the worst case, a complete failure to remodel.
But why, in the 21st century, do we rely on nature alone to heal our repaired and replaced tissues? Fortunately, the entire field of tissue regeneration is changing rapidly — and the Stone Research Foundation is at the forefront of this research.
We are now in, what I call, “The Anabolic Era of Orthopedics,” in which we add stem cells, growth factors, electrical stimulation and other factors to juice up the healing process. But stem cell science is advancing so rapidly that we now have off-the-shelf products with the highest desirable concentrations of stem cells and growth factors for every application.
Stem cells are pluripotent cells that produce a wide range of healing growth factors, along with anti-inflammatory, anti-scarring and antimicrobial agents. A 50-year-old person has one quarter the stem cells of a teenager.
Over the last few years in the Stone Clinic, we concentrated and combined patients’ own stem cells and growth factors with donor tissues before using them to rebuild ACLs and meniscus tissue. This year, we have off-the-shelf amniotic tissue with validated live cells and two-to-50 times the growth factor concentrations that we can obtain from the patient’s own blood. These tissues also contain millions of cells — many times more than the few found in older peoples’ bone and fat. These off-the-shelf cells are “immunoprivileged,” meaning they are not rejected (for the same reason a mother does not reject the baby she carries) and do not form tumors. Here is a short table of the stem cell sources today:
Pros: Very vascular with many cells.
Cons: Requires a surgical procedure; cell numbers decline with age.
Pros: Marrow cells are more similar to cartilage and bone.
Cons: Painful bone marrow biopsy procedure; cell numbers decline with age.
Pros: Easy access with a needle puncture; less expensive; growth factors two to five times normal.
Cons: Very few stem cells.
AMNIOTIC FLUID AND MEMBRANES
Pros: Two to 50 times growth factor concentration; very high concentration of stem cells; no second surgery.
Cons: Cost; many preparations have dead cells; quality control essential; if irradiated then low activity of growth factors.
Today, tissues transplanted in our clinic are pre-loaded with these amniotic growth factors and stem cells. We must now do the basic science to determine the optimal concentrations of these factors when infused into tissues and the clinical science to demonstrate if, and how much faster, the body heals with the use of these tissues. If effective enough, the application of stem cells and growth factors may quickly become widespread, leading to accelerated tissue repair.
Dr. Kevin R. Stone is an orthopedic surgeon at The Stone Clinic and chairman of the Stone Research Foundation in San Francisco.