Scientific American 2019-04

Illustration by Campbell Medical Illustration April 2019, ScientificAmerican.com 59

Heart cross section

Dead tissue (after heart attack)

Cell death and scarring Restored tissue

natives, such as pills, that were easier to take. Pharmaceutical
companies did not pursue it.
But for regenerating damaged cells, there are currently not a
lot of medical options. There have been many headlines about
stem cells, unspecialized cells that can, with the right cues, give
rise to the myriad highly differentiated cell types that make up
the human body. In theory, they could repair damaged parts.
Unfortunately, despite many years of clinical trials and other
tests, stem cell transplants remain challenged by a lack of effica-
cy and other serious concerns. The only wide use now is in bone
marrow transplants to treat blood cell diseases. But MSI-1436,

which has a proved safety record, could become valuable regen-

erative medicine for repairing the destruction from heart at-

tacks and potentially from other devastating diseases as well.

RESTORATION PROJECT

many animals have startling regenerative capabilities. Sala-

manders regrow entire limbs after amputation. The lamprey,

an eel-like fish, can repair a severed spinal cord. Zebra fish, a

popular aquarium fish species that is also broadly used in bio-

medical research, can regenerate damaged hearts, kidneys,

pancreases and appendages. Pick almost any tissue or organ,

Body Rebuilder

The ability of cells and organs to regenerate after injury is limited under normal

circumstances. After a heart attack, for instance, molecules called growth factors

and cytokines go to the heart to stimulate new growth, but their signals are blocked by

an enzyme. Dead heart cells are not replaced. In tests on mice with damaged hearts,

however, an injected compound called MSI-1436 inhibits the trouble-making enzyme.

The result is new heart muscle, pumping away.

2 The enzyme PTP1B

stops RTKs by cut-

ting away their

phosphate groups,

compon ents essen-

tial to the signaling

process. So re-

growth signals

never reach the

cell’s DNA.

Growth factors

and cytokines

MSI-1436 interferes

with PTP1B, keep-

ing the en zyme

from slicing off RTK

phosphates. So

re growth signals

move successfully

down a pathway

of proteins to the

cell’s DNA.

RTK

Phosphate

PTP1B

Cell membrane

Nuclear

membrane

Signaling

proteins

MSI-1436

Hindered Healing Healing Unblocked

(^1) Growth factors and cytokines attach to
proteins called RTKs, which help to send
regrowth signals into a cell.
The signal interrup-
tions mean dead
heart muscle cells
are not replaced by
new, healthy ones.
A scar of dead tissue
remains, weakening
the heart.
3 The signals kick-start
cell regeneration.
New heart muscle
grows to replace the
damage and restore
the organ’s blood
pumping ability.
DNA
DNA
2
3