Using MSCs derived from allogeneic bone marrow, AlloCure induces the cells to secrete a variety of growth factors and anti-inflammatory factors upon introduction to the damaged tissue, triggering repair through the growth of new cells and blood vessels. In November, the company presented findings of a Phase I safety and efficacy trial, showing that treatment not only lowered the incidence of AKI in cardiac surgery patients, but also shortened hospital stays and reduced hospital readmission rates. A Phase II study was underway as we went to press, with results from more than 200 patients expected in early 2014.  

 

Sweet surrender  

 

The so-called obesity epidemic has also triggered a growing problem—at least in the developed world—of diabetes, an area that is actively being explored by a number of companies.  

 

Type 1 diabetes is an autoimmune disease in which the insulin-producing cells in the pancreas are specifically attacked and destroyed. The autoimmune aspect of the condition complicates its treatment, explains Sarah Ferber, chief scientific officer and founder of White Plains, N.Y.-based Orgenesis, as any healthy pancreatic cells introduced into the body would simply be destroyed.

 

For this reason, Orgenesis focused its efforts on the conversion of autologous liver cells into insulin-producing cells that could be reimplanted in the liver to essentially replace the missing functions of the pancreas.  

 

"Liver is developmentally related to the pancreas and both tissues are sensitive to glucose," she explains. "In addition, liver has a substantial regenerative capacity and functional redundancy."  

 

While an unusual approach for most cell-based therapies, there is evolutionary precedent for this diabetic multi-organ shell game. Several organisms (e.g., eels and worms), Ferber explains, do not have a separate liver and pancreas, but rather a single organ called the hepatopancreas.

 

The company is still in the preclinical proof-of-concept phase, but has initiated conversations with regulators about proceeding to clinical trial.  

 

Like cardiac disease, diabetes does not simply limit its effects to the blood sugar and energy levels, but can also have secondary impacts, including a condition known as peripheral artery disease (PAD) where blood flow is blocked (often in the legs) and tissue damage can occur.  

 

Using mesenchymal-like stem cells derived from placenta, Pluristem developed a 3D culturing system that allowed it to "tune" the cells into producing a variety of cytokine cocktails that would facilitate repair in a variety of clinical conditions, including PAD. Aberman draws a parallel with the wine industry: "Change how you process grapes and you change the flavor of the wine and its quality. Likewise, if you change how you process the cells, you change how they function and their quality," he says.

 

 

At the Biotechnology Industry Organization's annual conference in June, the company introduced the results of preclinical studies in the use of the PLX system via intramuscular (IM) injection rather than through intravenous injection or direct application to the site of injury. According to Aberman, the ability to perform IM administration has significant market implications that potentially broaden not only to what diseases the product can be applied, but also who can apply them and how often.   

In July, the company announced a partnership with CPC Clinical Research to initiate Phase II studies of the PLX system in PAD, but perhaps the most dramatic moment came back in May, when the company announced the results of its compassionate use of PLX in a young girl who failed two bone marrow transplants and was expected to die. Within 10 days of the second and last injection of PLX, the patient's hematological patterns improved dramatically, and subsequent biopsies showed that cells from both bone marrow transplants were finally growing and maturing. After nine months, the patient was discharged from the hospital and is doing well.

 

"The physician treating the girl was in the same hospital where we had established our acute radiation models to develop PLX and he asked for compassionate use," explains Aberman. "You can do a lot in animals that may not work in humans. This worked."  

 

The rest of the story  

 

Other areas for which cell-based therapies are being developed by these and other companies include: Autoimmune conditions such as Crohn's disease and rheumatoid arthritis (e.g., Osiris, TiGenix, Mesoblast, TxCell); musculoskeletal conditions such as cartilage regeneration (e.g., Pluristem, Histogenics, Azellon Cell Therapeutics); ocular conditions such as AMD and retinopathy (e.g.,International Stem Cell, EyeCyte, Advanced Cell Technology); and oncological conditions such as neutropenia (e.g., Cellerant Therapeutics, Gamida Cell Therapy Technologies).

 

Lessons learned?  

 

Whether licking their wounds and dusting themselves off, or learning from the lessons of others who have fallen before them, the latest crop of regenerative medicine companies and scientists seem to be taking a much more methodical and deliberate approach to developing the next generation of cell-based therapies. It will take some time and patience, however, to see if those lessons have become ingrained.