Yet Another Stem Cell for Bone Growth

How many types of stem cells can grow bone? Apparently more than we knew.

Last week the California Institute for Regenerative Medicine (CIRM) announced a series of grants to four UCLA researchers—Drs. Bruno Peault and Chia Soo, professors of orthopedic surgery ($5, 391, 560), Dr. Noriyuki Kasahara, professor of digestive diseases ($3, 370, 607) and Dr. Sophie Deng, assistant professor of ophthalmology ($1, 654, 058).

PSC, MSC, ELA ….But wait, There’s Still More!

What caught our attention was Peault and Soo’s plan to study a form of stem cell called the Perivascular Stem Cell (PSC) which can be collected from fat tissue via liposuction. 

All currently available allograft or FDA approved stem cell products are based on the mesenchymal stem cell (MSC).  Soon, Alphatec Spine is expected to bring to market their allograft cell product based on yet another stem cell—the unique adult stem cell called the ELA stem cell. 

PSC, MSC and ELA.  How many more bone growth stem cell lineages, or partial lineages are there?

Cliff Notes Version of Stem Cells

Just to recap, stem cells are the original cell.  Or, at least, the cell that can metamorphose into a vast array of functional tissues.  In the beginning, meaning the point of embryonic inception, there are four pathways available for those first stem cells to follow—primordial germ cells, ectoderm cells, mesoderm cells and endoderm cells.  Each pathway leads to a wider range of specific tissue types.  The mesoderm pathway, for example, results in heart, muscle, blood or mesenchymal tissues.  The endoderm pathway takes cells to the intestine, pancreas, liver or lung cells.

Along any of those pathways—also called lineages—cells are at various stages of commitment.  Early along the lineage, they are largely uncommitted and could, through a variety of signals and other factors, become any one of a wide variety of tissues from that lineage.  Later in the lineage, they’re committed and are what they are.  Kind of like a typical 58-year-old publisher like me.

The first and still most popular and common form of stem cell for therapy is the mesenchymal stem cell which is part of the lineage that creates muscles, nerves and bone.  MSCs are adult stem cells.  They also, as they change, emit various signals which are themselves therapeutically valuable.  Some of these signals down regulate inflammation.  Other signals recruit more cells and growth factors.  Yet other signals are themselves growth factors for, depending on the environment, new bone or new nerve tissue growth.

Cousins of MSCs in Vascular Tissues!

So it is very interesting to read accounts of other cells which are also along the mesenchyme lineage and are probably new versions of MSCs—cousins perhaps.

Like MSCs, these newly identified precursor cells also have self-renewal and bone regenerative capabilities. Like MSC’s these newly identified cells are also isolated from adult donors. The ELA stem cell which Alphatec is working on is a highly concentrated form of these cells. They are derived using a proprietary isolation method that has the potential to yield up to six hundred times more cells than a similar volume of mesenchymal stem cells harvested from bone marrow. 

Since Alphatec is a spinal implant company, these early lineage cells are being targeted at patients with back problems requiring spine fusion, bone fractures, herniated disks and, potentially, osteoporosis. If successful, their study could provide an alternative to traditional bone grafting.

Pericytes

National Eye Institute/Wikimedia Commons

Last year at the New York Stem Cell Summit, Dr. Arnold Caplan, who wrote many of the seminal papers regarding MSCs and is the “father” of modern stem cell therapies, spoke about some obscure little critters called pericytes.

In Caplan’s view pericytes may well be the source of most MSCs.  And pericytes are everywhere in the human body including skeletal muscle, pancreas, adipose tissues, placental tissues, in vascular tissues and teeth.  Pericytes are not your father’s MSCs—which seemed to exist only in bone marrow or adipose tissues.  Pericytes are found in more areas of the body and they include perivascular cells.

UCLA researcher Bruno Peault has been writing for several years about perivascular cells (PSC).  He has shown in various articles that perivascular cells are myogenic in culture and in vivo.  Furthermore, regardless of their origin (Peault has used cells from cord blood, adipose tissue and other sources) they are osteogenic.  Other researchers have shown that PSCs are also chondrogenic and that they express MSC markers.  To take this even further, both Caplan and other researchers have been saying for a while now that blood vessel walls harbor a large amount of pericytes/progenitor cells that are very probably key to the origin of MSCs and other adult stem cells.

Stem Cells From Vascular Tissues in Fat

The PSC cells which UCLA researchers Peault and Soo are studying will be the subject of a three-year study which will put to the test a new combination of antibodies and cell sorting. The researchers hope the study will prospectively isolate these stem cells populations from fat.  The PSCs, like ELA or MSC, are also traveling along the lineage leading to bone, muscle or nerve tissues. 

PSC, however, have one important differentiating aspect.  Unlike traditional fat-derived MSCs, PSCs are not cultured for weeks before identification. This may be especially important from a therapeutic standpoint.  Using this approach, patients could in theory be treated more quickly and self-produce a higher yielding, purer form of stem cell population while also lowering the risk of contamination. In the UCLA protocol, the PSCs would be combined with a potent growth factor, NELL-1, to amplify the particular signal to “tell” PSC to form bone.

If successful, Peault and Soo hope to come up with a candidate drug or cell therapy or, at a minimum, make significant strides toward a drug candidate.  Of course, if Peault and Soo’s studies are successful then their new drug candidate would be eligible for the FDA regulatory gauntlet to be followed by the, umm, CMS (Centers for Medicare and Medicaid Services) keelhauling. 

It is in Peault and Soo’s plan to obtain PSC source material by way of fat liposuction from patients who are candidates for bone regeneration.  If successful, Peault and Soo would demonstrate a new method for rapidly isolating a new form of MSC and thereby increase the speed of new bone formation or at least prove to be faster than current methods of culture deriving MSCs from fat.  

UCLA Broad Stem Cell Center

Peault and Soo join a long list of scientists from the UCLA Broad Stem Cell Center who have, in the aggregate, received CIRM grants totaling more than $133 million. 

UCLA’s stem cell center was conceived in 2005 with a five-year $20 million seed commitment from UCLA. Funds from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center to the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.  The center and its 200 members are committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells.

Who’d have thought there were so many therapeutic stem cell candidates?  Or so many sources in the human body?